Triazolo[4,5-d]pyrimidine derivatives and their use as purinergic receptor antagonists

ABSTRACT

The use of a compound of formula (1): wherein R 1  is selected from H, alkyl, aryl, alkoxy, aryloxy, alkylthio, arylthio, halogen, CN, NR 5 R 6 , NR 4 CONR 5 R 6 , NR 4 CONR 5 R 6 NR 4 CO 2 R 7  and NR 4 SO 2 R 7 ; R 2  is selected from aryl attached via an unsaturated carbon; R 3  is selected from H, alkyl, COR 5 , CO 2 R 7 , CONR 5 R 6 , CONR 4 NR 5 R 6  and SO 2 R 7 ; R 4 , R 5  and R 6  are independently selected from H, alkyl and aryl or where R 5  and R 6  are in an NR 5 R 6  group, R 5  and R 6  may be linked to form a heterocyclic group, or where R 4 ,R 5  and R 6  are in a (CONR 4 NR 5 R 6 ) group, R 4  and R 5  may be linked to form a heterocyclic group; and R 7  is selected from alkyl and aryl, or a pharmaceutically acceptable salt thereof or prodrug thereof, in the treatment or prevention of a disorder in which the blocking of purine receptors, particularly adenosine receptors and more particularly A 2A  receptors, may be beneficial, particularly wherein said disorder is a movement disorder such as Parkinson&#39;s disease or said disorder is depression, cognitive or memory impairment, acute or chronic pain, ADHD or narcolepsy, or for neuroprotection in a subject; compounds of formula (I) for use in therapy; and novel compounds of formula (I) per se.

[0001] The present invention relates to triazolo[4,5-d]pyrimidinederivatives and their use in therapy. In particular, the presentinvention relates to the treatment of disorders in which the reductionof purinergic neurotransmission could be beneficial. The inventionrelates in particular to the blockade of adenosine receptors andparticularly adenosine A_(2A) receptors, and to the treatment ofmovement disorders such as Parkinson's disease.

[0002] Movement disorders constitute a serious health problem,especially amongst the elderly sector of the population. These movementdisorders are often the result of brain lesions. Disorders involving thebasal ganglia which result in movement disorders include Parkinson'sdisease, Huntington's chorea and Wilson's disease. Furthermore,dyskinesias often arise as sequelae of cerebral ischaemia and otherneurological disorders.

[0003] There are four classic symptoms of Parkinson's disease: tremor,rigidity, akinesia and postural changes. The disease is also commonlyassociated with depression, dementia and overall cognitive decline.Parkinson's disease has a prevalence of 1 per 1,000 of the totalpopulation. The incidence increases to 1 per 100 for those aged over 60years. Degeneration of dopaminergic neurones in the substantia nigra andthe subsequent reductions in interstitial concentrations of dopamine inthe striatum are critical to the development of Parkinson's disease.Some 80% of cells from the substantia nigra need to be destroyed beforethe clinical symptoms of Parkinson's disease are manifested.

[0004] Current strategies for the treatment of Parkinson's disease arebased on transmitter replacement therapy (Ldihydroxyphenylacetic acid(LDOPA)), inhibition of monoamine oxidase (e.g. Deprenyl®), dopaminereceptor agonists (e.g. bromocriptine and apomorphine) andanticholinergics (e.g. benztrophine, orphenadrine). Transmitterreplacement therapy in particular does not provide consistent clinicalbenefit, especially after prolonged treatment when “on-off” symptomsdevelop, and this treatment has also been associated with involuntarymovements of athetosis and chorea, nausea and vomiting. Additionallycurrent therapies do not treat the underlying neurodegenerative disorderresulting in a continuing cognitive decline in patients. Despite newdrug approvals, there is still a medical need in terms of improvedtherapies for movement disorders, especially Parkinson's disease. Inparticular, effective treatments requiring less frequent dosing,effective treatments which are associated with less severe side-effects,and effective treatments which control or reverse the underlyingneurodegenerative disorder, are required.

[0005] Blockade of A₂ adenosine receptors has recently been implicatedin the treatment of movement disorders such as Parkinson's disease(Richardson, P. J. et al., Trends Pharmacol. Sci. 1997, 18, 338-344) andin the treatment of cerebral ischaemia (Gao, Y. and Phillis, J. W., LifeSci. 1994, 55, 61-65). The potential utility of adenosine A_(2A)receptor antagonists in the treatment of movement disorders such asParkinson's Disease has recently been reviewed (Mally, J. and Stone, T.W., CNS Drugs, 1998, 10, 311-320).

[0006] Adenosine is a naturally occurring purine nucleoside which has awide variety of well-documented regulatory functions and physiologicaleffects. The central nervous system (CNS) effects of this endogenousnucleoside have attracted particular attention in drug discovery, owingto the therapeutic potential of purinergic agents in CNS disorders(Jacobson, K. A. et al., J. Med. Chems 1992, 35, 407-422). Thistherapeutic potential has resulted in considerable recent researchendeavour within the field of adenosine receptor agonists andantagonists (Bhagwhat, S. S.; Williams, M. E. Opin. Ther. Patents 1995,5,547-558).

[0007] Adenosine receptors represent a subclass (P₁) of the group ofpurine nucleotide and nucleoside receptors known as purinoreceptors. Themain pharmacologically distinct adenosine receptor subtypes are known asA₁, A_(2A), A_(2B) (of high and low affinity) and A₃ (Fredholm, B. B.,et al., Pharmacol. Rev. 1994, 46, 143-156). The adenosine receptors arepresent in the CNS (Fredholm, B. B., News Physiol. Sci., 1995, 10,122-128).

[0008] The design of P₁ receptor-mediated agents has been reviewed(Jacobson, K. A., Suzuki, F., Drug Dev. Res., 1997, 39, 289-300;Baraldi, P. G. et al., Curr. Med. Chem. 1995, 2, 707-722), and suchcompounds are claimed to be useful in the treatment of cerebral ischemiaor neurodegenerative disorders, such as Parkinson's disease (Williams,M. and Bumnstock, G. Purinergic Approaches Exp. Ther. (1997), 3-26.Editor. Jacobson, Kenneth A.; Jarvis, Michael F. Publisher: Wiley-liss,New York, N.Y.)

[0009] It has been speculated that xanthine derivatives such as caffeinemay offer a form of treatment for attention-deficit hyperactivitydisorder (ADHD). A number of studies have demonstrated a beneficialeffect of caffeine on controlling the symptoms of ADHD (Garfinkel, B. D.et al., Psychiatry, 1981, 26, 395-401). Antagonism of adenosinereceptors is thought to account for the majority of the behaviouraleffects of caffeine in humans and thus blockade of adenosine A_(2A)receptors may account for the observed effects of caffeine in ADSDpatients. Therefore a selective A_(2A) receptor antagonist may providean effective treatment for ADHD but without the unwanted side-effectsassociated with current therapy.

[0010] Adenosine receptors have been recognised to play an importantrole in regulation of sleep patterns, and indeed adenosine antagonistssuch as caffeine exert potent stimulant effects and can be used toprolong wakefulness Porkka-Heiskanen, T. et al., Science, 1997, 276,1265-1268). Recent evidence suggests that a substantial part of theactions of adenosine in regulating sleep is mediated through theadenosine A_(2A) receptor (Satoh, S., et al., Proc. Natl. Acad. Sci.,USA, 1996). Thus, a selective A_(2A) receptor antagonist may be ofbenefit in counteracting excessive sleepiness in sleep disorders such ashypersomnia or narcolepsy.

[0011] It has recently been observed that patients with major depressiondemonstrate a blunted response to adenosine agonist-induced stimulationin platelets, suggesting that a dysregulation of A_(2A) receptorfunction may occur during depression (Berk, M. et al, 2001, Eur.Neuropsycdopharnacol. 11, 183-186). Experimental evidence in animalmodels has shown that blockade of A_(2A) receptor function confersantidepressant activity (El Yacoubi, M et al. Br. J. Phannacol. 2001,134, 68-77). Thus, A_(2A) receptor antagonists may offer a novel therapyfor the treatment of major depression and other affective disorders inpatients.

[0012] The pharmacology of adenosine A_(2A) receptors has been reviewed(Ongini, E.; Fredholm, B. B. Trends PharmacoL Sci. 1996, 17(10),364-372). One potential underlying mechanism in the aforementionedtreatment of movement disorders by the blockade of A₂ adenosinereceptors is the evidence of a functional link between adenosine A_(2A)receptors to dopamine D₂ receptors in the CNS. Some of the early studies(e.g. Ferre, S. et al., Stimulation of high-affinity adenosine A₂receptors decreases the affinity of dopamine D₂ receptors in ratstriatal membranes. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 723841) havebeen summarised in two more recent articles (Puxe, K. et al., AdenosineAdenine Nucleotides Mol. Biol. Integr. Physiol., [Proc. Int. Symp.], 5th(1995), 499-507. Editors: Belardinelr, Luiz; Pelleg, Amir. Publisher:KIuwer, Boston, Mass.; Ferre, S. et al., Trends Neurosci. 1997, 20,482-487).

[0013] As a result of these investigations into the functional role ofadenosine A_(2A) receptors in the CNS, especially in vivo studieslinking A₂ receptors with catalepsy (Ferre et al., Neurosci. Leuf. 1991,130, 1624; Mandhane, S. N. et al., Eur. J. Pharmacol. 1997, 328,135-141) investigations have been made into agents which selectivelybind to adenosine A_(2A) receptors as potentially effective treatmentsfor Parkinson's disease.

[0014] While many of the potential drugs for treatment of Parkinson'sdisease have shown benefit in the treatment of movement disorders, anadvantage of adenosine A_(2A) antagonist therapy is that the underlyingneurodegenerative disorder may also be treated. The neuroprotectiveeffect of adenosine A_(2A) antagonists has been reviewed (Ongini, E.;Adami, M.; Ferri, C.; Bertorelli, R., Ann. N.Y. Acad. Sci. 1997,825(Neuroprotective Agents), 3048). In particular, compelling recentevidence suggests that blockade of A_(2A) receptor function confersneuroprotection against MP,IPinduced neurotoxicity in mice (Chen, J- F.,J. Neurosci. 2001, 21, RC143). In addition, several recent studies haveshown that consumption of dietary caffeine, a known adenosine A_(2A)receptor antagonist, is associated with a reduced risk of Parkinson'sdisease in man (Ascherio, A. et al, Ann Neurol., 2001, 50, 56-63; Ross GW, et al., JAMA, 2000, 283, 2674-9). Thus, A_(2A) receptor antagonistsmay offer a novel treatment for conferring neuroprotection inneurodegenerative diseases such as Parkinson's disease.

[0015] Xanthine derivatives have been disclosed as adenosine A₂ receptorantagonists as useful for treating various diseases caused byhyperfunctioning of adenosine A₂ receptors, such as Parkinson's disease(see, for example, EP-A-565377).

[0016] One prominent xanthine-derived adenosine A_(2A) selectiveantagonist is CSC [8-(3-chlorostyryl)caffeine] (Jacobson et al., FEBSLett., 1993, 323, 141-144).

[0017] Theophylline (1,3-dimethylxanthine), a bronchodilator drug whichis a mixed antagonist at adenosine A₁ and A_(2A) receptors, has beenstudied clinically. To determine whether a formulation of this adenosinereceptor antagonist would be of value in Parkinson's disease an opentrial was conducted on 15 Parkinsonian patients, treated for up to 12weeks with a slow release oral theophylline preparation (150 mg/day),yielding serum theophylline levels of 4.44 mg/L after one week. Thepatients exhibited significant improvements in mean objective disabilityscores and 11 reported moderate or marked subjective improvement (Mally,J., Stone, T. W. J. Pharin. Pharmacol. 1994, 46, 515-517).

[0018] KF 17837[E)-8-(3,4dimethoxystyryl)-1,3-dipropyl-7-methylxanthine] is a selectiveadenosine A_(2A) receptor antagonist which on oral administrationsignificantly ameliorated the cataleptic responses induced byintracerebroventricular administration of an adenosine A_(2A) receptoragonist, CGS 21680. KF 17837 also reduced the catalepsy induced byhaloperidol and reserpine. Moreover, KF 17837 potentiated theanticataleptic effects of a subthreshold dose of L-DOPA plusbenserazide, suggesting that KF 17837 is a centrally active adenosineA_(2A) receptor antagonist and that the dopaminergic function of thenigrostriatal pathway is potentiated by adenosine A_(2A) receptorantagonists (Kanda, T. et al., Eur. J. Pharmacol. 1994, 256, 263-268).The structure activity relationship (SAR) of KF 17837 has been published(Shimada, J. et al., Bioorg. Med. Chem. Lea. 1997, 7, 2349-2352). Recentdata has also been provided on the A_(2A) receptor antagonist KW-6002(Kuwana, Y et al., Soc. Neurosci. Abstr. 1997,23, 119.14; and Kanda, T.et al., Ann. Neurol. 1998,43(4), 507-513).

[0019] New non-xanthine structures sharing these pharmacologicalproperties include SCH 58261 and its derivatives (B3araldi, P. G. etal., Pyrazolo[4,3-e]-1,2,4-triazolo[1,5c]-pyrimidine Derivatives: Potentand Selective A_(2A) Adenosine Antagonists. J. Med Chem. 1996, 39,1164-71). SCH 58261(7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4triazolo[1,5-c]pyrimidine) is reported as effective in the treatment of movementdisorders (Ongini, E. Drug Dev. Res. 1997, 42(2), 63-70) and has beenfollowed up by a later series of compounds (Baraldi, P. G. et al., J.Med. Chem. 1998,41(12), 2126-2133).

[0020] The foregoing discussion indicates that a potentially effectivetreatment for movement disorders in humans would comprise agents whichact as antagonists at adenosine A_(2A) receptors.

[0021] It has now been found that triazolo[4,5-d]pyrimidine derivatives,which are structurally unrelated to known adenosine receptorantagonists, exhibit unexpected antagonist binding affinity at adenosine(P₁) receptors, and in particular at the adenosine A_(2A) receptor. Suchcompounds may therefore be useful for the treatment of disorders inwhich the blocldng of purine receptors, particularly adenosine receptorsand more particularly adenosine A_(2A) receptors, may be beneficial. Inparticular such compounds may be suitable for the treatment of movementdisorders, such as disorders of the basal ganglia which result indyskinesias. Disorders of of particular interest include Parkinson'sdisease, Alzheimer's disease, spasticity, Huntington's chorea andWilson's disease.

[0022] Such compounds may also be particularly suitable for thetreatment of depression, cognitive or memory impairment includingAlzheimer's disease, acute or chronic pain, ADSD and narcolepsy, or forneuroprotection.

[0023] According to the present invention there is provided the use of acompound of formula (I):

[0024] wherein

[0025] R₁ is selected from H, alkyl, aryl, alkoxy, aryloxy, alkylthio,arylthio, halogen, CN, NR₅R₆, NR₄COR₅, NR₄CONR₅R₆, NR₄CO₂R, andNR₄SO₂R₇;

[0026] R₂ is selected from aryl attached via an unsaturated carbon;

[0027] R₃ is selected from H, alkyl, COR₅, CO₂R₇, CONR₅R₆, CONR₄NR₅R₆and SO₂R₇;

[0028] R₄, R₅ and R₆ are independently selected from H, alkyl and arylor where R₅ and R₆ are in an NR₅R₆ group, R₅ and R₆ may be linked toform a heterocyclic group, or where R₄, R₅ and R₆ are in a (CONR₄NR₅R₆)group, R₄ and R₅ may be linked to form a heterocyclic group; and

[0029] R₇ is selected from alkyl and aryl,

[0030] or a pharmaceutically acceptable salt thereof or prodrug thereof,in the manufacture of a medicament for the treatment or prevention of adisorder in which the blQcking of purine receptors, particularlyadenosine receptors and more particularly A_(2A) receptors, may bebeneficial.

[0031] As used herein, the term “alkyl” means a branched or unbranched,cyclic or acyclic, saturated or unsaturated (e.g. alkenyl or alkynyl)hydrocarbyl radical which may be substituted or unsubstituted. Wherecyclic, the alkyl group is preferably C₃ to C₁₂, more preferably C₅ toC₁₀, more preferably C₅, C₆ or C₇. Where acyclic, the alkyl group ispreferably C₁ to C₁₀, more preferably C₁ to C₆, more preferably methyl,ethyl, propyl (n-propyl or isopropyl), butyl (n-butyl, isobutyl orterdary-butyl) or pentyl (including n-pentyl and iso-pentyl), morepreferably methyl. It will be appreciated therefore that the term“alkyl” as used herein includes alkyl (branched or unbranched), alkenyl(branched or unbranched), alkynyl (branched or unbranched), cycloalkyl,cycloalkenyl and cycloalkynyl.

[0032] As used herein, the term “lower alkyl” means methyl, ethyl,propyl (n-propyl or isopropyl) or butyl (n-butyl, isobutyl ortertiary-butyl).

[0033] As used herein, the term “aryl” means an aromatic group, such asphenyl or naphthyl, or a heteroaromatic group containing one or moreheteroatom(s), such as pyridyl, pyrrolyl, quinolinyl, furanyl, thienyl,oxadiazolyl, thiadiazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl,triazolyl, imidazolyl, pyrimidinyl, indolyl, pyrazinyl and indazolyl.

[0034] As used herein, the term “heteroaryl” means an aromatic groupcontaining one or more heteroatom(s) preferably selected from N, O andS, such as pyridyl, pyrrolyl, quinolinyl, fuiranyl, thienyl,oxadiazolyl, thiadiazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl,triazolyl, imidazolyl, pyrimidinyl, indolyl, pyrazinyl and indazolyl.

[0035] As used herein, the term “non-aromatic heterocyclyl” means anon-aromatic cyclic group containing one or more heteroatom(s)preferably selected from N, O and S, such as a cyclic amino group(including aziridinyl, azetidinyl, pyrrolidinyl, piperidyl, piperazinyl,morpholinyl) or a cyclic ether (including tetrahydrofuranyl).

[0036] As used herein, the term “alkoxy” means alkyl-O-. As used herein,the term “aryloxy” means aryl-O-.

[0037] As used herein, the term “halogen” means a fluorine, chlorine,bromine or iodine radical.

[0038] As used herein, the term “prodrug” means any pharmaceuticallyacceptable prodrug of a compound of the present invention.

[0039] Where any of R₁ to R₁₄ is selected from alkyl, alkoxy andalkylthio, particularly from alkyl and alkoxy, in accordance withformula (I) as defined above, then that alkyl group, or the alkyl groupof the alkoxy or alkylthio group, may be substituted or unsubstituted.Where any of R₁ to R₁₄is selected from aryl, aryloxy and arylthio,particularly from aryl and aryloxy, in accordance with formula (I) asdefined above, then said aryl group, or the aryl group of the aryloxygroup, may be substituted or unsubstituted. Where R₅ and R₆, or R₄ andR₅, are linked to form a heterocyclic group, the heterocyclic group maybe substituted or unsubstituted. Where substituted, there will generallybe 1 to 3 substituents present, preferably 1 substituent. Substituentsmay include:

[0040] carbon-containing groups such as

[0041] alkyl,

[0042] aryl, (e.g. substituted and unsubstituted phenyl (includingalkylphenyl, alkoxyphenyl and halophenyl),

[0043] arylalkyl; (e.g. substituted and unsubstituted benzyl);

[0044] halogen atoms and halogen containing groups such as

[0045] haloalkyl (e.g. trifluoromethyl),

[0046] haloaryl (e.g. chlorophenyl);

[0047] oxygen containing groups such as

[0048] alcohols (e.g. hydroxy, hydroxyalkyl, hydroxyaryl,(aryl)(hydroxy)alkyl),

[0049] ethers (e.g. alkoxy, aryloxy, alkoxyalkyl, aryloxyalkyl,alkoxyaryl, aryloxyaryl),

[0050] aldehydes (e.g. carboxaldehyde),

[0051] ketones (e.g. alkylcarbonyl, arylcarbonyl, alkylcarbonylalkyl,alkylcarbonylaryl, arylcarbonylalkyl, arylcarbonylaryl,arylalkylcarbonyl, arylalkylcarbonylalkyl, arylalkylcarbonylaryl)

[0052] acids (e.g. carboxy, carboxyalkyl, carboxyaryl),

[0053] acid derivatives such as esters (e.g. alkoxycarbonyl,aryloxycarbonyl, alkoxycarbonylalkyl, aryloxycarbonylalkyl,alkoxycarbonylaryl, aryloxycarbonylaryl, alkylcarbonyloxy,alkylcarbonyloxyalkyl), amides

[0054] (e.g. aminocarbonyl, mono- or di-alkylaminocarbonyl,cyclicaminocarbonyl, aminocarbonylalkyl, mono- ordi-alkylaminocarbonylakyl, arylaminocarbonyl or arylalkylaninocarbonyl,alkylcarbonylamino, arylcarbonylamino or arylalkylcarbonylamino),carbamates

[0055] (eg. alkoxycarbonylamnino, aryloxycarbonylamino,

[0056] arylaikyloxycarbonylamino, aminocarbonyloxy, mono- ordi-alkylaminocarbonyloxy, arylaminocarbonyloxy or

[0057] arylalkylaminocarbonyloxy) and ureas

[0058] (eg. mono- or di-alkylaminocarbonylamino, arylaminocarbonylaminoor

[0059] arylalkylaminocarbonylarnino);

[0060] nitrogen containing groups such as

[0061] amines (e.g. amilno, mono- or diallylamino, cyclicamino,arylamino, aminoalkyl, mono- or dialkylaminoalkyl),

[0062] azides,

[0063] nitriles (e.g. cyano, cyanoalkyl),

[0064] nitro,

[0065] sulfonamides (e.g. aminosulfonyl, mono- or di-alkylaminosulfonyl, mono- or di-arylaminosulfonyl, alkyl- or aryl-sulfonyl amino,alkyl- or aryl-sulfonyl(alkyl)amino, alkyl- oraryl-sulfonyl(aryl)amino);

[0066] sulfur containing groups such as

[0067] thiols, thioethers, sulfoxides, and sulfones

[0068] (e.g. alkylthio, alkylsulfinyl, alkylsulfonyl, alkylthioalkyl,alkylsumfinylalkyl, alkylsulfonylalkyl, arylthio, arylsulfinyl,arylsulfonyl, arylthioalkyl, arylsulfinylalkyl, arylsulfonylalkyl)

[0069] and heterocyclic groups containing one or more, preferably one,heteroatom,

[0070] (e.g. thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl,thiazolyl, isothiazolyl, oxazolyl, oxadiazolyl, thiadiazolyl,aziridinyl, azetidinyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl,imidazolinyl, pyrazolidinyl, tetrahydrofuranyl, pyranyl, . pyronyl,pyridyl, pyrazinyl, pyridazinyl, piperidyl, hexahydroazepinyl,piperazinyl, morpholinyl, thianaphthyl, benzofuranyl, isobenzofuranyl,indolyl, oxyindolyl, isoindolyl, indazolyl, indolinyl, 7-azaindolyl,benzopyranyl, coumarinyl, isocoumarinyl, quinolinyl, isoquinolinyl,naphthridinyl, cinnolinyl, quinazolinyl, pyridopyridyl, benzoxazinyl,quinoxalinyl, chromenyl, chrornanyl, isochromanyl, phthalazinyl andcarbolinyl).

[0071] Where any of R₁ to R₁₄ is selected from aryl or from anaryl-containing group such as aryloxy or arylthio, preferred substituentgroup(s) are selected from halogen, alkyl (substituted or unsubstituted;and where substituted particularly from alkoxyalkyl, hydroxyallyl,aminoalkyl and haloalkyl), hydroxy, alkoxy, CN, NO₂, amines (includingamino, mono- and di-alkylamino), alkoxycarbonyl, aminocarbonyl,carboxaamido, sulfonamido, alkoxycarbonylamino and aryl, andparticularly from unsubstituted alkyl, substituted alkyl (includingalkoxyalkyl and aminoalkyl), halogen and amines.

[0072] In one embodiment, where any of R₁ to R₁₄ is directly substitutedby an alkyl substituent group, or by an alkyl-containing substituentgroup (such as alkoxy or alkylcarbonylamino for example), then the alkylmoiety of the substituent group directly attached to any of R₁ to R₁₄may be further substituted by the substituent groups hereinbeforedescribed and particularly by halogen, hydroxy, alkoxy, CN, amines(including amino, mono- and di-alkyl amino) and aryl.

[0073] In a furter embodiment, where any of R₁ to R₁₄ is directlysubstituted by an aryl substitutent group, or by an aryl-containingsubstituent group (such as aryloxy or aylaminocarbonylamino forexample), then the aryl moiety of the substituent group directlyattached to any of R₁ to R₁₄ may be further substituted by thesubstituent groups hereinbefore described and particularly by halogen,alkyl (substituted or unsubstituted; and where substituted particularlyfrom alkoxyalkyl, hydroxyalkyl, aminoalkyl and haloalkyl), hydroxy,alkoxy, CN, NO₂, amines (including amino, mono- and dialkylamino),alkoxycarbonyl, aminocarbonyl, carboxamido, sulfonamido,alkoxycarbonylamino and aryl. In a further embodiment, said aryl moietyis substituted by halogen, alkyl (including CF₃), hydroxy, alkoxy, CN,amines (including amino, mono- and di-alkyl amino) and NO₂. In a furtherembodiment, said aryl moiety is substituted by unsubstituted alkyl,substituted alkyl (particularly alkoxyalkyl and aminoalkyl), halogen andamines.

[0074] The terms “directly substituted” and “directly attached”, as usedherein, mean that the substituent group is bound directly to any of R₁to R₁₄ without any intervening divalent atoms or groups.

[0075] In the compounds of formula (I), R₁ is selected from H, alkyl(including branched and unbranched alkyl, substituted and unsubstitutedalkyl, and cyclic and acyclic alkyl), aryl (including heteroaryl),alkoxy, aryloxy, alkylthio, arylthio, halogen, CN, NR₅R₆ (includingNH₂), NR₄COR₅, NR₄CONR₅R₆, NR₄CO₂R₇ and NR₄SO₂R₇.

[0076] In one embodiment, the compounds of formula (I) are those whereinR₁ is selected from alkyl (including branched and unbranched alkyl,substituted and unsubstituted alkyl, and cyclic and acyclic alkyl), aryl(including heteroaryl), alkoxy, aryloxy, alkylthio, arylthio, halogen,CN, NR₅R₆ (including NH₂), NR₄COR₅, NR₄CONR₅R₆, NR₄CO₂R₇ and NR₄SO₂R₇.

[0077] Preferably, R₁ is selected from alkyl (including branched andunbranched alkyl, substituted and unsubstituted alkyl, and cyclic andacyclic alkyl), alkoxy, alkylthio, NRsR (including NH₂), NR₄COR₅,NR₄CONR₅R₆, NR₄CO₂R₇ and NR₄SO₂R₇preferably from NR₅R₆ (including NH₂),NR₄COR₅, NR₄CONR₅R_(6,) NR₄CO₂R₇ and NR₄SO₂R₇, more preferably fromNR₅R₆ (including NH₂) and NR₄COR₅, more preferably from NR₅R₆ (includingNH₂) and most preferably from NH₂.

[0078] Where R₁ is selected from NR₅R₆, in one embodiment R₅ and R₆ areindependently selected from hydrogen, alkyl and aryl, preferably fromhydrogen.

[0079] Where R₁ is selected from NR₄COR₅, in one embodiment R₄ ishydrogen.

[0080] Where R₁ is selected from alkyl, R₁ is preferably C₁₋₆ alkyl,more preferably C₁₋₆ saturated alkyl, and more preferably lower alkyl.In one embodiment, R₁ is selected from substituted alkyl, particularlyhaloalkyl (including CF₃) and arylalkyl (including heteroarylalkyl), andparticularly haloalkyl (including CF₃).

[0081] Preferably, R₂ is a heteroaryl group, and preferably a heteroarylgroup which is attached to the pyrimidine ring of formula (I) such thatat least one heteroatom is adjacent to the unsaturated carbon atomattached to said pytimidine ring. Preferably, R₂ is an N, O orS-containing heteroaryl group. R₂ may contain one or more heteroatom(s)selected from N, O and S.

[0082] In one embodiment, the aryl group of R₂ (including wherein R₂ isa heteroaryl group) is not ortho,ortho-disubstituted. Preferably, thearyl group of R₂ (including wherein R₂ is a heteroaryl group) is notsubstituted at either ortho position. As used herein, reference toortho-substitution of the R₂ group means the ortho positions of the R₂group relative to the point of attachment of R₂ to the pytimidine moietyof formula (D.

[0083] In a preferred embodiment, R₂ is selected from furyl (including2-furyl), thienyl (including 2-thienyl), pyridyl (including 2-pyridyl),thiazolyl (including 2- and 5-thiazolyl), pyrazolyl (including3-pyrazolyl), triazolyl (including ⁴-triazolyl), pyrrolyl (including2-pyrrolyl) and oxazolyl (including 5-oxazolyl). In a flrher embodiment,R₂ is selected from 2-flryl, 2-thienyl, ²-thiazolyl, 2-pyridyl,3-pyrazolyl, 2-pyrrolyl, 4-triazolyl and 5-oxazolyl. In a futterpreferred embodiment, R₂ is selected from furyl, thienyl, pyridyl,thiazolyl and pyrazolyl, and particularly from 2-furyl, 2-thienyl,2-thiazolyl, 2-pyridyl and ³-pyrazolyl. In a further embodiment, R₂ isselected from furyl, thienyl and pyridyl, preferably 2-frryl, 2-thienyland 2-pyridyl. In a particularly preferred embodiment, R₂ is selectedfrom furyl, and preferably from 2-furyl, substituted or unsubstituted.

[0084] Where R₂ is other than a heteroaryl group, R₂ is preferablyphenyl.

[0085] In the compounds of formula (I), R₃ is selected from H, alkyl(including branched and unbranched alkyl, substituted and unsubstitutedalkyl, cyclic and acyclic alkyl), COR₅, CO₂R₇, CONR₅R₆, CONR₄NR₅R₆ andSO₂R₇.

[0086] Where R₃ is selected from alkyl, R₃ is preferably acyclic alkyl,preferably acyclic C₁₋₆ alkyl (including alkenyl and alkynyl),preferably acyclic C₁₋₆ saturated alkyl, preferably lower alkyl. In oneembodiment, R₃ is selected from substituted or unsubstituted methyl,ethyl and propyl (n-propyl or isopropyl) groups.

[0087] Where R₃ is selected from alkyl, particularly from saturatedacyclic C₁₋₆ alkyl, particularly from lower alkyl and particularly frommethyl, ethyl and propyl, it is preferred that R₃ is substituted alkyl.Preferred substituents are aryl (including heteroaryl), cycloalkyl,non-aromatic heterocyclyl, CN, COR₅, C₂R₅, CONR₅R₆, CONR₄NR₅R₆ andC(═NR₄)NR₅R₆, preferably aryl (including heteroaryl), CONR₅R₆, CO₂R₅ andCOR₅ (preferably wherein R₅ is aryl), more preferably aryl (includingheteroaryl), CONR₅R₆ and COR₅, more preferably aryl (includingheteroaryl) and CONR₅R₆, and most preferably aryl (includingheteroaryl).

[0088] Where R₃ is selected from arylalkyl (including heteroarylalkyl),the aryl (including heteroaryl) group may be unsubstituted, orsubstituted as defined in detail below in respect of the group referredto as RI₁. Preferably, the arylalkyl (including heteroarylalkyl group)is an arylmethyl (including heteroarylmethyl) group. The preferred arylgroups are set out below in detail in respect of the group referred toas Ar.

[0089] Where R₃ is selected from CONR₅R₆, R₅ and R₆ are selected from H,alkyl (including substituted alkyl such as arylalkyl (includingheteroarylalkyl)) and aryl (including heteroaryl) or R₅ and R₆ may belinked to form a heterocyclic ring. In one embodiment, R₅ and R₆ areselected from unsubstituted alkyl and arylalkyl (includingheteroarylalkyl). Said aryl groups may be substituted or unsubstituted.In a preferred embodiment one of R₅ and R₆ is hydrogen. In a fiutherpreferred embodiment, R₅ is H and R₆ is selected from arylalkyl(including heteroarylalkyl), preferably arylmethyl (includingheteroarylmethyl).

[0090] In a preferred embodiment, R₃ is selected from H and substitutedalkyl, preferably wherein said alkyl is substituted by aryl (includingheteroaryl) or CONR₅R₆,and preferably by aryl (including heteroaryl),and more preferably by substituted Myl (including heteroaryl).In oneembodiment, R₃ is selected from (CR₉R₁₀)_(n)R₈ wherein n is 1 to 6(preferably n is 1, 2 or 3, and preferably n is 1), R₉ and R₁₀ areindependently selected from H, alkyl and aryl, and Rs is selected fromaryl (including heteroaryl), cycloalkyl, non-aromatic heterocyclic, CN,COR₅, CO₂R_(5,) CONR₅R₆,CONR₄NR₅R₆ and C(═NR₄)NR₅R₆,preferably aryl(including heteroaryl), CONR₅R₆,CO₂R₅ and COR₅ (preferably wherein R₅ isaryl), more preferably aryl (including heteroaryl), CONR₅R₆ and CO₂R₅,more preferably aryl (including heteroaryl) and CONR₅R₆, and mostpreferably aryl (including heteroaryl). Preferably, R₉ and R₁₀ areindependently selected from H and alkyl (preferably acyclic saturatedC₁₋₆ alkyl, preferably lower alkyl, preferably methyl, ethyl or propyl),more preferably H. Preferably, at least one of R₉ and R₁₀ is hydrogen,and preferably both R₉ and R₁₀ are hydrogen.

[0091] Where R₉ is aryl (including heteroaryl), the aryl (includingheteroaryl) group may be unsubstituted, or may be substituted as definedin detail below for R₁₁. The preferred aryl groups are set out below indetail in respect of the group referred to as Ar.

[0092] Where R₈ is selected from CONR₅R₆, R₅ and R₆ are selected from H,alkyl (including substituted alkyl such as arylalkyl (includingheteroarylalkyl)) and aryl (including heteroaryl) or R₅ and R₆ may belinked to form a heterocyclic ring. Ih one embodiment, one or both of R₅and R₆ are selected from unsubstituted alkyl and arylalkyl (includingheteroarylalkyl). In a fiwder embodiment, at least one of R₅ and R₆ isselected from aryl (including heteroaryl). Said aryl group may besubstituted or unsubstituted. In a preferred embodiment, one of R₅ andR₆ is hydrogen.

[0093] Where R₈ is selected from COR₅, R₅ is preferably aryl (includingheteroaryl).

[0094] Where R₈ is selected from CO₂R_(5,) R₅ is preferably alkyl oraryl.

[0095] In a further preferred embodiment, R₃ is selected from H and(CR₉R₁₀)_(n)R₈, more preferably from (CH₂)R₈, preferably wherein R₈ isselected from aryl (including heteroaryl) and CONR₅R₆, more preferablywherein R₈ is selected from aryl (including heteroaryl), and morepreferably wherein R₈ is selected from substituted aryl (includingheteroaryl).

[0096] In a further embodiment, R₃ is selected from (CR₉R₁₀)_(n)R₁₁wherein R₉, R₁₀ and n are as defined above and R₁₁ is selected from thegroup consisting of substituted aryl (including heteroaryl) groups,preferably mono-, di- or tri-substituted aryl (including heteroaryl)groups represented by the formula Ar(R₁₂)_(a)(R₁₃)_(b)(R₁₄)_(c) whereinAr is an aryl (including heteroaryl) group; wherein R₁₂, R₁₃ and R₁₄ aresubstituent group(s), the same or different; and wherein a, b and c are0 or 1 such that a+b+c≧1.

[0097] In one embodiment, the group Ar is selected from phenyl. In analternative embodiment, the group Ar is selected from heteroaryl groupssuch as those described hereinabove, preferably from mono or bicyclicheteroaryl groups, more preferably from pyridyl (including 2-pyridyl,3-pyridyl and 4pyridyl, preferably 2-pyridyl), indolyl (including2-indolyl, 3-indolyl, 4indolyl, 5-indolyl, 6-indolyl and 7-indolyl),furyl (including 2-furyl and 3-furyl, preferably 2-furyl), thienyl(including 2-thienyl and 3-thienyl, preferably 2-thienyl), isoindolyl,indolinyl, isoxazolyl, oxazolyl, thiazolyl, pyrazinyl, pyrimidinyl,quinolinyl, benzoxadiazolyl, benzothiadiazolyl, benzotriazolyl,indazolyl, benzodioxolyl and dihydrobenzofuranyl, more preferably frompyridyl (preferably 2-pyridyl), indolyl, furyl (preferably 2-furyl) andthienyl (preferably 2-thienyl), and most preferably from pyridyl(preferably 2-pyridyl), furyl (preferably 2-furyl) and thienyl(preferably 2-thienyl).

[0098] In one embodiment, the group Ar is selected from phenyl, pyridyl(preferably 2-pyridyl), furyl (preferably 2-filryl), thienyl (preferably2-thienyl) and indolyl, and particularly from phenyl, pyridyl(preferably 2-pyridyl), furyl (preferably 2-frryl) and thienyl(preferably 2-thienyl).

[0099] The substituent groups R₁₂, R₁₃ and R₁₄ may be selected from anyof the substituent groups described herein above.

[0100] In a preferred embodiment, R₁₂, R₁₃ and R₁₄ are selected fromNR₅R₆ (including NH₂, and NHR₅) alkyl (substituted or unsubstituted;preferably C₁₋₆ acyclic alkyl), alkoxy (including fluoroalkoxy), halogen(including F, Cl, Br and I), NO₂, CN, hydroxy, NHOH, CHO, CONR₅R₆,CO₂R₅,NR₄COR₅ preferably NHCOR₅), NR₄CO₂R₇ (preferably NHCO₂R₇), NR₄SO₂R₇(preferably NHSO₀₂ ₇), OCO₂R₇ and aryl (including heteroaryl).

[0101] In a more preferred embodiment, R₁₂, R₁₃ and R₁₄ are selectedfrom NR₅R₆ (including NH₂ and NHR₅), alkyl (substituted orunsubstituted; and preferably C₁₋₆ acyclic saturated alkyl) and halogen(preferably P or Cl, particularly P).

[0102] In a particularly preferred embodiment, R₁₂, R₁₃ and R₁₄ areselected from NR₅R₆ (including NH₂ and NHR_(5,) preferably NH₂) andalkyl (substituted or unsubstituted; preferably C₁₋₆ acyclic saturatedalkyl);

[0103] Where R₁₂, R₁₃ and R₁₄ are selected from substituted alkyl, saidalkyl is preferably selected from alkoxyalkyl, hydroxyalkyl, aminoalkyl(including NH₂-alkyl, mono-alkylaminoalkyl and di-alkylaminoalkyl),haloalkyl (particularly fluoroalkyl (including CF₃)), cyanoalkyl,alkylthioalkyl, alkylcarboxyaminoalkyl, alkoxycarbonylaminoalkyl andalkylsulfonylamino, more preferably from alkoxyalkyl, hydroxyalkyl,aminoalkyl and haloalkyl (particularly fluoroalkyl (including CF₃)) andmost preferably from alkoxyalkyl and aminoalkyl.

[0104] In one embodiment, the substituent groups R₁₂, R₁₃ and R₁₄ areselected from halogen, al.lyl (including CF₃), hydroxy, alkoxy,alkylthio, CN, amines (including amino, monoand di-alkyl amino) and NO₂.

[0105] Where the Ar group is phenyl, the phenyl ring may be mono-, di-or tri-substituted, preferably wherein the substituent group is selectedfrom NR₅R₆,alkyl, alkoxy, halogen, NO₂, CN, hydroxy, CONR₅R₆,CO₂R_(5,)NR₄COR₅, NR₄CO₂R₇, NR₄SO₂R₇ and OCO₂R₇, as described above, and morepreferably from NR₅R₆ (including NH₂ and NHR₅, and preferably NH₂),alkyl (substituted or unsubstituted; preferably C₁₋₆ acyclic saturatedalkyl; and, where substituted, preferably from alkoxyalkyl,hydroxyalkyl, aminoalkyl and haloalkyl (particularly fluoroalkyl(including CF₃)), and more preferably from alkoxyalkyl and aminoalkyl)and halogen (preferably P or Cl, particularly F). Where (a+b+c) is 2 or3, it is preferred that at least one of the substituent groups is NR₅R₆,particularly NH₂.

[0106] Where the Ar group is pyridyl, the pyridyl group (which ispreferably a 2-pyridyl group) is preferably mono-substituted, preferably6-substituted. The preferred substituent group(s) are selected fromalkyl (including substituted and unsubstituted, saturated andunsaturated (such as alkenyl, including vinyl); and preferably C₁₋₆acyclic alkyl), alkoxy, halogen, aryl, NO₂, NHOH and CHO, as describedabove, and more preferably from alkyl (substituted or unsubstituted;preferably C₁₋₆ acyclic saturated alkyl; and, where substituted,preferably from alkoxyalkyl, hydroxyalkyl, aminoallyl and haloalkyl(particularly fluoroalkyl (including CF₃)), and more preferably fromalkoxyalkyl and aminoalkyl).

[0107] In a preferred embodiment R₃ is selected from CHR₉R₁₁ wherein R₉and R₁₁ are as defined above, and preferably wherein Ar is substitutedpyridyl or substituted phenyl. Where Ar is substituted phenyl,preferably at least one of R₁₂ and R₁₃, or at least one of R₁₂, R₁₃ andR₁₄, is NR₅R₆,preferably NH₂.

[0108] In the compounds of formula (I), R₄, R₅ and R₆ are independentlyselected from H, alkyl (including branched and unbranched allyl,substituted and unsubstituted alkyl, cyclic and acyclic alkyl) and aryl(including heteroaryl) or where R₅ and R₆ are in any NR₅R₆ group, R₅ andR₆ may be linked to form a heterocyclic ring, or where R₄, R₅ and R₆ arein a (CONR₄NR₅R₆) group, R₄ and R₅ may be linked to form a heterocyclicring.

[0109] In the compounds of formula (I), R₇ is selected from alkyl(including branched and unbranched alkyl, substituted and unsubstitutedalkyl, cyclic and acyclic alkyl) and aryl (including heteroaryl).

[0110] Where R₄ to R₇ are independently selected from alkyl, preferablyR₄ to R₇ are selected from C₁₋₆ alkyl, preferably C₁₋₆ saturated alkyland more preferably from lower alkyl.

[0111] Where R₅ and R₆, or R₄ and R₅, are linked to form a heterocyclicring said heterocyclic ring may be saturated, partially unsaturated oraromatic, and is preferably saturated.

[0112] Said heterocyclic ring is preferably a 5, 6 or 7-membered ring,preferably a 5 or 6-membered ring, and may contain one or more flirtherheteroatom(s) preferably selected from N, O and S.

[0113] In a preferred embodiment, R₁ is NH₂, R₂ is 2-furyl and R₃ isarylmethyl (including heteroarylmethyl).

[0114] In one embodiment of the invention, the compounds of formula (I)are selected from those set out in claim 41.

[0115] In a further embodiment of the invention, the compounds offormula (I) are selected from those set out in claim 42.

[0116] Where chiral the compounds of formula (I) may be in the form of aracemic mixture of pairs of enantiomers or in enantiomerically pureform.

[0117] According to a further aspect of the present invention there isprovided a method of treating or preventing a disorder in which theblocking of purine receptors, particularly adenosine receptors and moreparticularly adenosine A_(2A) receptors, may be beneficial, the methodcomprising administration to a subject in need of such treatment aneffective dose of a compound of formula (I) or a pharmaceuticallyacceptable salt or prodrug thereof.

[0118] The disorder may be caused by the hyperfunctioning of the pufinereceptors.

[0119] The disorders of particular interest are those in which theblocking of purine receptors, partiucularly adenosine receptors and moreparticularly adenosine A_(2A) receptors, may be beneficial. These mayinclude movement disorders such as Parkinson's disease, drug-inducedParkinsonism, post-encephalitic Parkinsonism, Parkinsonism induced bypoisoning (for example MIP, manganese, carbon monoxide) andpost-traumatic Parkinson's disease (punch-drunk syndrome).

[0120] Other movement disorders in which the blocking of purinereceptors, may be of benefit include progressive supernuclear palsy,Huntingtons disease, multiple system atrophy, corticobasal degeneration,Wilsons disease, Hallerrorden-Spatz disease, progressive pallidalatrophy, Dopa-responsive dystonia-Parkinsonism, spasticity or otherdisorders of the basal ganglia which result in abnormal movement orposture. The present invention may also be effective in treatingParkinson's with on-off phenomena; Parkinson's with freezing (end ofdose deterioration); and Parkinson's with prominent dyskinesias.

[0121] The compounds of formula (I) may be used or administered incombination with one or more additional drugs useful in the treatment ofmovement disorders, such as L-DOPA or a dopamine agonist, the componentsbeing in the same formulation or in separate formulations foradministration simultaneously or sequentially.

[0122] Other disorders in which the blocking of purine receptors,particularly adenosine receptors and more particularly adenosine A_(2A)receptors may be beneficial include acute and chronic pain; for exampleneuropathic pain, cancer pain, trigeminal neuralgia, migraine and otherconditions associated with cephalic pain, primary and secondaryhyperalgesia, inflammatory pain, nociceptive pain, tabes dorsalis,phantom limb pain, spinal cord injury pain, central pain, post-herpeticpain and IIfV pain; affective disorders including mood disorders such asbipolar disorder, seasonal affective disorder, depression, manicdepression, atypical depression and monodepressive disease; central andperipheral nervous system degenerative disorders including corticobasaldegeneration, demyelinating disease (multiple sclerosis, disseminatedsclerosis), Freidrich's ataxia, motoneurone disease (amyotrophic lateralsclerosis, progressive bulbar atrophy), multiple system atrophy,myelopathy, radiculopathy, peripheral neuropathy (diabetic neuropathy,tabes dorsalis, druginduced neuropathy, vitamin deficiency), systemiclupus erythamatosis, granulomatous disease, olivo-ponto-cerebellaratrophy, progressive pallidal atrophy, progressive supranuclear palsy,spasticity; schizophrenia and related pyshoses; cognitive disordersincluding dementia, Alzheimers Disease, Frontotemporal dementia,multi-infarct dementia, AIDS dementia, dementia associated withHuntingtons Disease, Lewy body dementia, senile dementia, age-relatedmemory impairment, cognitive impairment associated with dementia,Korsakoff syndrome, dementia pugilans; attention disorders such asattention-deficit hyperactivity disorder (ADHD), attention deficitdisorder, minimal brain dysfunction, brain-injured child syndrome,hyperkinetic reaction childhood, and hyperactive child syndrome; centralnervous system injury including traumatic brain injury, neurosurgery(surgical trauma), neuroprotection for head injury, raised intracranialpressure, cerebral oedema, hydrocephalus, spinal cord injury; cerebralischaemia including transient ischaemic attack, stroke (thromboticstroke, ischaemic stroke, embolic stroke, haemorrhagic stroke, lacunarstroke) subarachnoid haemorrhage, cerebral vasospasm, neuroprotectionfor stroke, peri-natal asphyxia, drowning, cardiac arrest, subduralhaematoma; myocardial ischaemia; muscle ischaemia; sleep disorders suchas hypersomnia and narcolepsy; eye disorders such as retinalischaemia-reperfusion injury and diabetic neuropathy; cardiovasculardisorders such as claudication and hypotension; and diabetes and itscomplications.

[0123] According to a ftrther aspect of the present invention there isprovided use of a compound of formula (I) or a pharmaceuticallyacceptable salt or prodrug thereof in the manufacture of a medicamentfor the treatment or prevention of movement disorders in a subject.

[0124] According to a furter aspect of the invention there is provided amethod of treating or preventing movement disorders comprisingadministration to a subject in need of such treatment an effective doseof a compound of formula (I) invention or a pharmaceutically acceptablesalt or prodrug thereof.

[0125] According to a further aspect of the invention there is provideduse of a compound of formula (I) or a pharmaceutically acceptable saltor prodrug thereof in the manufacture of a medicament forneuroprotection in a subject.

[0126] According to a further aspect of the invention there is provideda method of neuroprotection comprising administration to a subject inneed of such treatment an effective dose of a compound of formula (I) ora pharmaceutically acceptable salt or prodrug thereof.

[0127] The medicament for or method of neuroprotection may be of use inthe treatment of subjects who are suffering from or at risk from aneurodegenerative disorder, such as a movement disorder.

[0128] According to a further aspect of the invention, there is providedfor use in therapy a compound of formula (I), or a pharmaceuticallyacceptable salt or prodrug thereof.

[0129] The present invention may be employed in respect of a human oranimal subject, more preferably a mammal, more preferably a humansubject.

[0130] According to a ftutber aspect of the present invention, there isprovided a compound of formula (I), per se, other than compounds whereinR₁ is H and R₃ is selected from methyl, more preferably other thancompounds wherein R₁ is H and R₃ is selected from unsubstituted loweralkyl, more preferably other than compounds wherein R₁ is H and R₃ isselected from unsubstituted allyl, and more preferably other thancompounds wherein R₁ is H.

[0131] According to a further aspect of the present invention, there isprovided a compound of formula (I), per se, other than compounds whereinR₃ is methyl, preferably other than compounds wherein R₃ isunsubstituted lower alkyl and more preferably other than compoundswherein R₃ is unsubstituted alkyl.

[0132] According to a frrther aspect of the invention there is provideda method of preparing the novel compounds of formula (1). Compounds offormula (1) may be prepared according to conventional synthetic methods.For example compounds of formula (1) where R₁ is NH₂ may be synthesisedby standard methods such as those illustrated in Reaction Scheme 1.

[0133] Compounds of formula (4) where R₃ is alkyl (including arylalkyl,heteroarylalkyl and (CR₉R₁₀)_(n)CO₂R₅) may be prepared from compounds offormula (3) by standard methods such as reaction with an appropriatealkyl halide, or substituted alkyl halide in the presence of a suitablebase such as sodium hydride.

[0134] Compounds of formula (4) where R₃ is (CR₉R₁₀)_(n)CONR₅R₆ or(CR₀R₁₀)_(n)CONR₄NR₅R₆ may be prepared from compounds of formula (4)where R₃ is (CR₉R₁₀)_(n)CO₂R₅ by standard methods such as directreaction with an appropriate amine or hydrazine or by initial hydrolysisof the ester group CO₂R₅ to a carboxylic acid followed by reaction withan appropriate amine or hydrazine in the presence of a standard couplingreagent such as DCC.

[0135] Compounds of formula (4) where R₃ is (CR₉R₁₀)_(n)C(═NR₄)NR₅R₆ maybe prepared from compounds of formula (4) where R₃ is(CR₉R₁₀)_(n)CN bystandard methods such as treatment with an appropriate amine in thepresence of trimethyl aluminium.

[0136] Compounds of formula (4) where R₃ is(CR₉R₁₀)_(n)CN may beprepared from compounds of formula (3) by standard methods such astreatment with an appropriate substituted alkyl halide in the presenceof a suitable base such as sodium hydride.

[0137] Compounds of formula (4) where R₃ is CONR₅R₆ or CONR₄NR₅R₆ may beprepared from compounds of formula (3) by standard methods such astreatment with an appropriate isocyanate (R₅NCO or R₆NCO) or carbamoylchloride (R₅R₆NCOCl or R₅R₆NR₄NCOCl).

[0138] Compounds of formula (4) where R₃ is COR₅, CO₂R₇ or SO₂R₇ may beprepared from compounds of formula (3) by standard methods such astreatment with an appropriate acid chloride (R₅COCl), chloroformate(ClCO₂R₇) or sulphonyl chloride (R₇SO₂Cl) in the presence of a suitablebase such as triethylamine.

[0139] Compounds of formula (3) may be prepared from the known chlorocompound of formula (2) by standard methods such as aryl or heteroarylcoupling reactions. Suitable aryl or heteroaryl coupling reactions wouldinclude reaction with an appropriate aryl or heteroarylboronic acidderivative, an aryl or heteroaryl trialkylstannane derivative or an arylor heteroarylzinc halide derivative in the presence of a suitablecatalyst such as a palladium complex.

[0140] Compounds of formula (3) may also be prepared from compounds offormula (7) by standard methods such as treatment with isoamyl nitrite.Compounds of formula (7) are either known in the literature or may beprepared from compounds of formula (6) by standard methods such asreduction with hydrogen in the presence of a suitable catalyst such asPd. Compounds of formula (6) are either known in the literature or maybe prepared from the known compound of formula (5) by standard methodssuch as aryl or heteroaryl coupling reactions as described above.

[0141] Compounds of formula (1) where R₁ is NR₅R₆ may be prepared fromcompounds of formula (4) by standard methods such as reductive aminationwith an appropriate aldehyde or ketone, or by treatment with anappropriate alkyl halide in the presence of a suitable base.

[0142] Compounds of formula (1) where R₁ is NR₄CONR₅R₆, wherein R₄ is H,may be prepared from compounds of formula (4) by standard methods suchas treatment with an appropriate isocyanate R₅NCO or R₆NCO) or carbamoylchloride R₅R₆NCOCl). Compounds of formula (1) where R₁ is NR₄CONR₅R₆,wherein R₄ is alkyl, may be prepared as described above having firstperformed an additional alkylation step as described above.

[0143] Compounds of formula (I) where R₁ is NR₄COR₅, NR₄CO₂R₇ orNR₄SO₂R₇, wherein R₄ is H, may be prepared from compounds of formula (4)by standard methods such as treatment with an appropriate acid chloride(R₅COCl), chloroformate (ClCO₂R₇) or sulphonyl chloride (R₇SO₂Cl) in thepresence of a suitable base. Compounds of formula (I) where R₁ isNR₄COR₅, NR₄CO₂R₇ or NR₄SO₂R₇, wherein R₄ is alkyl may be prepared asdescribed above having first performed an additional alkylation step asdescribed above.

[0144] Compounds of formula (I) where R₁ is NH₂ may also be synthesisedby standard methods such as those illustrated in Reaction Scheme 2.

[0145] Compounds of formula (4) where R₃ is alkyl (including arylalkyl,heteroarylalkyl and (CR₉R₁₀)_(n)CO₂R₅) may be prepared from compounds offormula (10) by standard methods such as aryl or heteroaryl couplingreactions as described above. Compounds of formula (10) where R₃ isalkyl are either known in the literature or may be prepared by methodsanalogous to those described in the literature. For example compounds offormula (10) where R₃ is alkyl may be prepared from compounds of formula(9) where R₃ is alkyl by standard methods such as treatment with isoamylnitrite. Compounds of formula (9) where R₃ is alkyl are either known inthe literature or may be prepared by methods analogous to thosedescribed in the literature such as the treatment of the known compoundof formula (8) with an appropriate amine in a suitable solventpreferably at elevated temperature.

[0146] Compounds of formula (1) where R₁ is NH₂ may also be synthesisedby standard methods such as those illustrated in Reaction Scheme 3.

[0147] Compounds of formula (4) where R₃ is alkyl (including arylalkyl,heteroarylalkyl and (CR₉R₁₀)_(n)CO₂R₅) may be prepared from compounds offormula (15) where R₃ is alkyl by standard methods such as treatmentwith isoamyl nitrite. Compounds of formula (15) where R₃ is alkyl may beprepared from compounds of formula (14) where R₃ is alkyl by standardmethods such as reduction with hydrogen in the presence of a suitablecatalyst such as Pd. Compounds of formula (14) where R₃ is alkyl areeither known in the literature or may be prepared from compounds offormula (13), where X is a suitable leaving group such as a tosylate ortriflate group, by standard methods such as treatment with a suitableamine in the presence of a suitable base such as triethylamine.Compounds of formula (13) where X is a suitable leaving group are eitherknown in the literature or may be prepared from compounds of formula(12) by standard methods such as treatment with tosyl chloride ortriflic anhydride in the prence of a suitable base such as triethylamineor 2,6-dimethylpyridine. Compounds of formula (12) are either known inthe literature or may be prepared from the known compound of formula(11) by standard methods such as aryl or heteroaryl coupling reactionsas described above.

[0148] Other compounds of formula (1) may be prepared by standardmethods such as those illustrated in Reaction Scheme 4.

[0149] Compounds of formula (1) where R₁ is H, alkyl or aryl may beprepared from compounds of formula (16) where R₁ is H, alkyl or aryl bystandard methods such as aryl or heteroaryl coupling reactions asdescribed above. Compounds of formula (16) where R₁ is H, alkyl or arylare either known in the literature or may be prepared by methodsanalogous to those described in the literature.

[0150] Compounds of formula (1) where R₁ is alkoxy, aryloxy, alkylthio,arylthio, CN or NRs may be prepared from compounds of formula (1) whereR₁ is halogen by standard methods such as nucleophilic displacementusing an appropriate nucleophilic reagent such as an alcohol, thiol,cyanide or amine (NR₅R₆) in the presence of a suitable base if required.Compounds of formula (1) where R₁ is halogen may be prepared fromcompounds of formula (16) where R₁ is halogen as described above.Compounds of formula (16) where R₁ is halogen are either known in theliterature or may be prepared by methods analogous to those described inthe literature.

[0151] Compounds of formula (I) where R₁ is NR₄CONR₅R₆, NR₄COR₅,NR₄CO₂R₇ or NR₄SO₂R₇, wherein R₄ is alkyl or aryl, may be prepared fromcompounds of formula (1) where R₁ is NR₅R₆,wherein R₅ is H and R₆ isalkyl or aryl, by the methods described above.

[0152] In certain cases it may be advantageous to prepare a compound offormula (1) where R₃ is selected to perform the function of a protectinggroup, for example a suitable protecting group would be a benzyl groupor substituted benzyl group such as a 3,4-dimethoxybenzyl group.Compounds of this nature may prepared as described above and theprotecting group R₃ may be removed by standard methods such as treatmentwith, for example, TFA to give a compound of formula (1) where R₃ is H.Compounds of formula (1) where R₃ is H may then be used to prepare othercompounds of formula (1), where R₃ is as previously defined, by themethods described above.

[0153] In the compounds of formula (1) the groups R₁, R₂ and R₃ may befurther substituted as defined above and it will be appreciated by thoseskilled in the art that suitable substituent groups may be introduceddirectly according to the methods described above or alternatively maybe introduced by further functionalisation of substituent groups whichthemselves are introduced directly. For example where the group R₁, R₂or R₃ contains a nitro substituent this may be reduced by standardmethods to an amino group. The resulting amino group may then be furthertransformed by a variety of standard methods known to those skilled inthe art to an alternative functional group such as an amide, urea,carbamate, sulphonamide or alkylamine.

[0154] According to a further aspect of the invention, there is provideda pharmaceutical composition comprising a compound of formula (I) incombination with a pharmaceutically acceptable carrier or excipient anda method of making such a composition comprising combining a compound offormula (I) with a pharmaceutically acceptable carrier or excipient.

[0155] The pharmaceutical compositions employed in the present inventioncomprise a compound of the present invention, or pharmaceuticallyacceptable salts or prodrugs thereof, and may also contain apharmaceutically acceptable carrier and optionally other therapeuticingredients known to those skilled in the art. The term,“pharmaceutically acceptable salts”, refers to salts prepared frompharmaceutically acceptable non-toxic acids including inorganic acidsand organic acids.

[0156] Where the compounds of formula (I) are basic, salts may beprepared from pharmaceutically acceptable non-toxic acids includinginorganic and organic acids. Such acids include acetic, benzenesulfonic,benzoic, camphorsulfonic, citric, ethenesulfonic, fumaric, gluconic,glutamic, hippuric, hydrobromic, hydrochloric, isethionic, lactic,maleic, malic, mandelic, methanesulfonic, mucic, nitric, pamoic,pantothenic, phosphoric, succinic, sulfuric, tartaric, oxalic,p-toluenesulfonic and the like. Particularly preferred are hydrochloric,hydrobromic, phosphoric, and sulfuric acids, and most particularlypreferred is the hydrochloride salt.

[0157] Any suitable route of administration may be employed forproviding the patient with an effective dosage of a compound of thepresent invention. For example, oral, rectal, parenteral (intravenous,intramuscular), transdermal, subcutaneous, and the like may be employed.Dosage forms include tablets, troches, dispersions, suspensions,solutions, capsules, patches, and the like. The most suitable route inany given case will depend on the severity of the condition beingtreated. The most preferred route of administration of the presentinvention is the oral route. The compositions may be convenientlypresented in unit dosage form and prepared by any of the methods wellknown in the art of pharmacy.

[0158] In practical use, the compounds can be combined as the activeingredient in intimate admixture with a pharmaceutical carrier accordingto conventional pharmaceutical compounding techniques. The carrier maytake a wide variety of forms depending on the form of preparationdesired for administration, e.g. oral or parenteral (e.g. intravenous).In preparing the compositions for oral dosage form, any of the usualpharmaceutical media may be employed as carriers, such as, for example,water, glycols, oils, alcohols, flavouring agents, preservatives,colouring agents, and the like in the case of oral liquid preparations(such as suspensions, solutions and elixirs) or aerosols; or carrierssuch as starches, sugars, micro-crystalline cellulose, diluents,granulating agents, lubricants, binders, disintegrating agents, and thelike may be used in the case of oral solid preparations such as, forexample, powders, capsules, and tablets, with the solid oralpreparations being preferred over the liquid preparations. The mostpreferred solid oral preparation is tablets.

[0159] Because of their ease of administration, tablets and capsulesrepresent the most advantageous oral dosage unit form in which casesolid pharmaceutical carriers are employed. If desired, tablets may becoated by standard aqueous or non-aqueous techniques.

[0160] In addition to the common dosage forms set out above, thecompounds may also be administered by controlled release means and/ordelivery devices such as those described in U.S. Pat. Nos. 3,845,770;3,916,899; 3,536,809; 3,598,123; 3,630,200; 4,008,719; 4,687,660; and4,769,027, the disclosures of which are hereby incorporated byreference.

[0161] Pharmaceutical compositions employed in the present inventionsuitable for oral administration may be presented as discrete units suchas capsules, cachets, or tablets, or aerosol sprays each containing apredetermined amount of the active ingredient as a powder or granules, asolution or a suspension in an aqueous liquid, an oil-in-water emulsion,or a water-inoil liquid emulsion. Such compositions may be prepared byany of the methods of pharmacy, but all methods include the step ofbringing the active ingredient into association with the carrier whichconstitutes one or more necessary ingredients. In general, thecompositions are prepared by uniformly and intimately admixing theactive ingredient with liquid carriers or finely divided solid carriersor both, and then, if necessary, shaping the product into the desiredpresentation.

[0162] For example, a tablet may be prepared by compression or moulding,optionally with one or more accessory ingredients. Compressed tabletsmay be prepared by compressing in a suitable machine the activeingredient in a free-flowing form such as powder or granules, optionallymixed with a binder, a lubricant, an inert diluent, and/or a surfaceactive or dispersing agent. Moulded tablets may be made by moulding in asuitable machine a mixture of the powdered compound moistened with aninert liquid diluent.

[0163] The invention is further defined by reference to the followingexamples. It will be apparent to those skilled in the art that manymodifications, both to materials and methods, may be practised withoutdeparting from the purpose and interest of this invention.

EXAMPLES Synthetic Examples

[0164] The invention is illustrated with reference to the followingExamples, as set out in Table 1. TABLE 1 Example Structure Compound Name1

7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 2

N,N-bis(2-fluorobenzyl)-3-(2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine- 5-amine 3

3-(2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 4

7-(2-furyl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 5

3-(3-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 6

methyl 3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-yl)methylbenzoate 7

3-(3,5-dimethoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 8

3-(5-chloro-2-thienyl)methyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 9

N-(3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-yl)methyl)phenyl-(1-methyl-1H-imidazol-4- yl)sulphonamide 10

5-amino-N-benzyl-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-ylcarboxamide 11

7-(2-furyl)-3-(3-methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 12

7-(2-furyl)-3-(2-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 13

3-(2-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 14

ethyl 5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[45-d]pyrimidin-3-ylacetate15

3-(3-cyanobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 16

7-(2-furyl)-3-(3-(3-pyridyl)propyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 17

7-(2-furyl)-3-(3-trifluoromethylbenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 18

7-(2-furyl)-3-(3-hydroxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 19

7-(5-methyl-2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 20

3-(2-fluorobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 21

7-(1H-pyrazol-3-yl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 22

3-(2-fluorobenzyl)-7-(5-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 23

7-(2-furyl)-3-(3-methylbenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 24

7-(2-furyl)-3-(2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 25

7-(2-furyl)-3-(3-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 26

(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)acetic acid27

3-(3-chlorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 28

3-(2-fluorobenzyl)-7-(1H-pyrazol-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 29

7-(2-furyl)-3-methyl-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 30

(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)acetamide31

(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-N-(3-chlorophenyl)acetamide32

7-(2-furyl)-3-(6-methoxy-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 33

7-(2-furyl)-3-(2-thienylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 34

3-(2-fluorobenzyl)-7-(2-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 35

3-(2-fluorobenzyl)-7-(2-thienyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 36

3-(3-aminobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 37

7-(2-furyl)-3-(6-methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 38

3-(2-fluorobenzyl)-7-(5-methyl-2-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 39

tert-butyl N-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)benzyl)carbamate 40

3-(2,5-dimethoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 41

3-(2,6-difluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 42

3-(2-fluorobenzyl)-7-(4-methyl-2-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 43

7-(2-thienyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 44

6-chloro-N-(7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)pyridine-3-carboxamide 45

3-(3-nitrobenzyl)-7-(5-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 46

3-(3-aminomethylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 47

3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-N,N-dimethylbenzamide48

3-(3-aminobenzyl)-7-(2-thienyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 49

3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-N-methylbenzamide50

3-(3-aminobenzyl)-7-(5-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 51

3-(2-fluoro-5-methoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 52

(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-N-(2-pyridyl)acetamide53

(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-N-(2-pyridylmethyl)acetamide54

(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-N-phenylacetamide55

3-(3,5-dinitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 56

7-(5-methyl-2-furyl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 57

3-(2,3-difluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 58

3-(2,4-difluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 59

7-(5-methyl-2-furyl)-3-(6-methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 60

3-(2,6-difluorobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 61

7-(5-methyl-2-furyl)-3-(2-thienylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 62

3-(3-chlorobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 63

7-(2-furyl)-3-(4-methoxy-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 64

7-(2-furyl)-3-(2-methylbenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 65

3-(2,5-difluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 66

7-(2-furyl)-3-(2-methoxy-5-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 67

3-(5-amino-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)- N-methylbenzamide 68

N-(3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzyl)acetamide 69

3-(2-fluorobenzyl)-7-(5-oxazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 70

3-(4-chloro-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 71

3-(6-fluoro-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 72

3-(2-methoxybenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 73

tert-butyl N-(3-(5-amino-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)benzyl)carbamate 74

3-(2-aminobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine hydrochloride 75

3-(3,5-diaminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 76

3-(3-aminomethylbenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine hydrochloride 77

7-(2-furyl)-3-(2-methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 78

3-(2-fluoro-5-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 79

3-(5-amino-2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 80

3-(2-fluorobenzyl)-7-(1H-triazol-4-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 81

3-(6-chloro-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 82

7-(5-methyl-2-furyl)-3-(6-phenyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 83

3-(3-aminobenzyl)-7-(2-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 84

3-(5-amino-2-fluorobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine hydrochloride 85

N-(3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzyl)-3-methylbutanamide 86

7-(5-methyl-2-furyl)-3-(4-nitro-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 87

3-(4-hydroxylamino-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 88

7-(2-furyl)-3-(2-methyl-3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 89

3-(3-amino-2-methylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 90

3-(3-amino-4-methylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 91

3-(3,5-dimethylisoxazol-4-ylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 92

7-(2-furyl)-3-(3-methyl-2-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 93

3-cyclohexylmethyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 94

7-(2-furyl)-3-(3-methyl-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 95

7-(2-furyl)-3-(3-methyl-2-pyridylmethy)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 96

7-(2-furyl)-3-(5-methyl-2-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 97

3-(4-amino-3-methylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 98

3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzoic acid 99

3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzamide 100

7-(2-furyl)-3-(2-methylthiazol-4-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 101

3-(3-aminomethylbenzyl)-7-(1H-pyrazol-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 102

3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-N-isopropyl-N-methylbenzamide 103

3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-N-isopropylbenzamide104

3-(2-amino-5-methylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 105

3-(4-cyano-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 106

7-(2-furyl)-3-(5-methyl-2-pyrazinylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 107

7-(2-furyl)-3-(8-quinolinylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 108

7-(2-furyl)-3-(2-phenylthiazol-4-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 109

7-(4-methyl-2-thiazolyl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 110

3-(4-chloro-3-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 111

3-[1,2,5-benzoxadiazol-5-yl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 112

7-(2-furyl)-3-(6-methoxymethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 113

3-benzyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 114

3-(3-amino-4-chlorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 115

7-(2-furyl)-3-(4-nitro-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 116

7-(2-furyl)-3-(4-hydroxylamino-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 117

7-(2-furyl)-3-(6-methyl-4-nitro-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 118

7-(2-furyl)-3-(4-hydroxylamino-6-methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 119

3-(4-chloro-2-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 120

3-(2-amino-4-chlorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 121

3-(4-cyanobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 122

3-(3,4-dimethoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine trifluoroacetate salt 123

7-(5-methyl-2-furyl)-3-(3-methyl-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 124

3-(4-amino-3-methylbenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 125

7-(2-furyl)-3-(5-methyl-3-oxazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 126

7-(2-furyl)-3-(3-methyl-4-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 127

3-(1,2,5-benzothiadiazol-4-ylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 128

7-(2-furyl)-3-(2-pyrazinylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 129

3-(4-fluoro-3-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 130

3-(3-nitrobenzyl)-7-phenyl-3H- [1,2,3]triazolo[4,5-d]pyrimidine-5-amine131

7-(2-furyl)-3-(4-methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 132

tert-butyl N-(2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)- 4-pyridylmethyl)carbamate133

7-(2-furyl)-3-(3-methoxy-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 134

7-(2-furyl)-3-(4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 135

3-(6-ethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 136

3-(2-ethyl-4-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 137

tert-butyl 7-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)indole-1-carboxylate 138

tert-butyl 4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)indole-1-carboxylate 139

7-(2-furyl)-3-(4-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 140

tert-butyl N-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)benzyl)carbamate 141

3-(4-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 142

tert-butyl 5-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)indole-1-carboxylate 143

tert-butyl N-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)- 2-fluorophenyl)carbamate144

3-(4-aminomethylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 145

7-(5-ethyl-2-furyl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 146

tert-butyl 6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)indole-1-carboxylate 147

3-(4-amino-3-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 148

tert-butyl (4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-3,5-difluorophenyl)carbonate 149

3-(2,6-difluoro-4-hydroxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 150

3-(3-aminobenzyl)-7-(5-ethyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 151

3-(3-aminobenzyl)-7-phenyl-3H- [1,2,3]triazolo[4,5-d]pyrimidine-5-amine152

7-(2-furyl)-3-(6-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 153

7-(2-furyl)-3-(5-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 154

7-(2-furyl)-3-(7-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 155

3-(5-fluoro-2-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 156

3-(2,6-difluoro-4-methoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 157

tert-butyl N-(2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)benzyl)carbamate 158

3-(1H-benzothiazol-5-ylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 159

7-(2-furyl)-3-(2-methoxy-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 160

N-(3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)phenylacetamide 161

3-(2-aminomethylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 162

3-(3-(N,N-dimethylamino)benzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 163

3-(4-difluoromethoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 164

7-(2-furyl)-3-(6-phthalimidomethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 165

3-(3-amino-4-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 166

3-(2,3-dihydrobenzofuran-5-ylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 167

3-(5-bromo-2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 168

7-(2-furyl)-3-(2,3,5-trifluorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 169

3-(2-fluoro-5-iodobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 170

7-(2-furyl)-3-(2-furylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 171

3-(2-amino-5-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 172

tert-butyl (5-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)- 2-nitrophenyl)carbonate173

3-(4-amino-3-hydroxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 174

3-(4-amino-3-fluorobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 175

3-(3-aminobenzyl)-7-(1H-pyrazol-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 176

7-(2-furyl)-3-(3-hydroxy-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 177

N-(6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2- pyridylmethyl)acetamide178

N-(2-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzyl)acetamide 179

7-(2-furyl)-3-(3-thienylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 180

3-(3-amino-2-methylbenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 181

7-(2-furyl)-3-(3-methyl-2-thienyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 182

3-(6-allyloxymethyl-2-pyridylmethyl)-N,N-diallyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 183

3-(6-methoxymethyl-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 184

3-(4-aminobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 185

3-(6-allyloxymethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5- amine 186

3-(6-allyloxymethyl-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 187

7-(2-furyl)-3-(3-isopropyl-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 188

7-(2-furyl)-3-(quinolin-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 189

7-(2-furyl)-3-(4-(N-methylamino)benzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 190

2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-(6-methyl-2-pyridyl)propanone 191

3-(3-aminobenzyl)-7-(1H-pyrrol-2-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 192

3-(3-nitrobenzyl)-7-(2-pyridyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 193

N-(4-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)acetamide 194

7-(2-furyl)-3-(4-nitro-2-(2- trimethylsilylethoxy)methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 195

3-(3-ethyl-4-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 196

7-(2-furyl)-3-(2-(2-thienylethyl))-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 197

7-(2-furyl)-3-(6-isopropyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 198

7-(2-furyl)-3-(1-(2H-tetrahyropyran-2-yl)indazol-5-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 199

3-(4,6-diisopropyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 200

7-(2-furyl)-3-(5-indazolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 201

7-(2-furyl)-3-(2-hydroxy-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 202

7-(2-furyl)-3-(6-vinyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 203

tert-butyl 5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-carboxylate 204

tert-butyl 3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)indole-1-carboxylate 205

6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)pyridine-2-carboxaldehyde206

tert-butyl 2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)indole-1-carboxylate 207

3-(2-indolylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 208

3-(5-ethyl-2-thienylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 209

7-(2-furyl)-3-(3,4-methylenedioxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 210

3-(4-amino-3-ethylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 211

2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-phenylethanone212

N-(3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidine-3-methyl)phenyl)thiophene-2-carboxamide 213

7-(2-furyl)-3-(6-hydroxymethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine hydrochloride214

N-(3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidine-3-methyl)phenyl)-3,3-dimethylbutanamide 215

N-(3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidine-3-methyl)phenyl)cyclopropanecarboxamide 216

7-(2-furyl)-3-(6-n-propyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 217

7-(2-furyl)-3-(6-isobutyloxymethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 218

3-(6-bromomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 219

3-(4-amino-3-isopropylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 220

3-(6-cyanomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 221

3-(4-hydroxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 222

2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-(4-nitrophenyl)ethanone223

4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylacetyl)-benzonitrile224

N-(3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)propanesulphonamide 225

N-(3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)-5-chloro-2- thiophenesulphonamide 226

7-(2-furyl)-3-(6-(N-methylamino)methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine hydrochloride227

2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-(4-(N,N-diethylamino)phenyl)ethanone 228

7-(2-furyl)-3-(6-isopropyl-3-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 229

2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-(4-methoxyphenyl)ethanone230

tert-butyl 7-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-5-chloroindole-1-carboxylate 231

3-(5-chloro-7-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 232

N-(3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)-3,5-dimethylisoxazol-4- ylsulphonamide 233

3-(6-(N,N-dimethylamino)methyl-2- pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 234

7-(2-furyl)-3-(6-methylthiomethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 235

2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-(2-nitrophenyl)ethanone236

N-(3-(5-amino-7-(2-furyl)-3H- [1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)-1,2-dimethyl-1H-imidazol- 4-ylsulphonamide 237

N,N-bis(6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2-pyridylmethyl)methanesulphonamide 238

7-(2-furyl)-3-(6-methylsulphonylmethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 239

N-(6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2- pyridylmethyl)-N-methylmethanesulphonamide 240

3-(3-aminobenzyl)-7-(4,5-dimethyl-2-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 241

3-(4-amino-2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 242

2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-indanone243

7-(2-furyl)-3-(5-methyl-7-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 244

N-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2- methylphenyl)formamide245

2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-phenylpropanone246

3-(7-fluoro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 247

7-(2-furyl)-3-(6-isopropoxymethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 248

3-(6-ethyl-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 249

3-(4-chloro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 250

3-(7-bromo-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 251

3-(6-chloro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 252

3-(3-(4-fluorobenzylamino)benzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 253

3-(6-ethoxy-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 254

3-(6-ethoxy-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 255

3-(3-(2-pyridylmethylamino)benzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 256

7-(2-furyl)-3-(1-(4- trifluoromethylphenyl)ethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 257

3-(6-fluoro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 258

3-(5-fluoro-2-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 259

3-(3,5-dimethyl-4-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 260

3-(1-(3-fluorophenyl)ethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 261

3-(7-chloro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 262

3-(4-amino-3,5-dimethylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 263

3-(1-(3-aminophenyl)ethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 264

7-(2-furyl)-3-(6-(2-methoxyethyl)-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 265

7-(2-furyl)-3-(1-(5,6-dimethyl-2-pyridyl)propyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 266

3-(3-nitrobenzyl)-7-(1H-pyrazol-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine hydrochloride 267

7-(5-methyl-2-furyl)-3-(2-methyl-3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 268

7-(5-methyl-2-furyl)-3-(4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 269

tert-butyl N-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3- ylmethyl)phenyl)-N-methylcarbamate270

tert-butyl 2-(5-amino-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yl)pyrrole-1- carboxylate 271

7-(4,5-dimethylthiazol-2-yl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 272

3-(2-fluoro-4-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine 273

tert-butyl 7-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-5-methylindole-1-carboxylate 274

ethyl N-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)methyl)- 2-methylphenyl)carbamate

[0165] The general synthetic methods used for the preparation of theseExamples are set out below as Methods A to BH. Table 2 sets out theMethod used for each Example, together with analytical data.

[0166] HPLC is carried out using the following conditions: Column.Waters Xterra RP 18 (50×4.6 mm); Particle size 5 μM; Mobile phase MeOH:10 mM aq NH₄OAc (pH 7 buffer); Gradient 50:50 isocratic for 1 min. thenlinear gradient 50:50 to 80:20 over 5 min. then 80:20 isocratic for 3min.; Flow rate 2.0 mL/min.; Detection wavelength λ=230 nM. Retentiontimes are provided.

[0167] Method A

[0168] 7-(2-Furyl)-1H-[1,2,3]Triazolo[4,5-D]Pyrimidine-5-Amine (Example1)

[0169] A solution of7-chloro-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (570 mg, 3.34 mmol)in N-methyl-2-pyrrolidinone (4 mL) was treated with PdCl₂(PPh₃)₂ (117mg, 0.17 mmol) and 2-(tributylstannyl)furan (1.05 mL, 1 mmol), stirredat 80° C. for 5 h, diluted with EtOAc, filtered through a silica pad andconcentrated in vacuo. The residue was triturated with diethyl ether andthe title compound isolated as a yellow solid (438 mg, 65%).

[0170] Method B

[0171]3-(2-Fluorobenzyl)-7-(2-Furyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidine-5-Amine(Example 3)

[0172] A solution of7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (101 mg, 0.5mmol) in DMF (2 mL), at 0° C., was treated with NaH (20 mg, 60%, 0.5mmol), stirred for 20 mins then treated with 2-fluorobenzyl bromide (60μL, 0.5 mmol). The reaction mixture was allowed to warm to roomtemperature, stirred for 1 h, quenched with water, extracted with EtOAc,dried (MgSO₄) and concentrated in vacuo. The crude product was purifiedby chromatography (EtOAc:Heptane, 1:4—EtOAc:Heptane, 2:1) to giveN,N-bis(2-fluorobenzyl)-3-(2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(Example 2) (28 mg, 11%) as a yellow solid and the title compound (34mg, 22%) as a yellow solid.

[0173] Method C

[0174]3-(3-Aminobenzyl)7(2-Furyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimiidine-5-Amine(Example 5)

[0175] A solution of7-(2-furyl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrinidine-5-amine(152 mg, 0.45 mmol) in EtOH (2 mL) at 50° C. was treated with a solutionof SnCl₂ (305 mg, 1.35 miol) in conc. HCl (0.7 mL), stirred for 2 h,cooled, diluted with water, basified to pH 10 (5-M, NaOH) and filteredto give the titlecompound (127 mg, 92%) as a white solid.

[0176] Method D

[0177]N-(3-(5-Amino-7-(2-Furyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidin-3-Yl)Methyl)Phenyl-(1-Methyl-1H-Imidazol-4-Yl)Sulphonamide(Example 9)

[0178] A solution of3-(3-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(125 mg, 0.41 mmol) in DMF (2 mL) was treated with Et₃N (85 SAL, 0.61mmol) and 1-methylimidazole-4-sulphonyl chloride (74 mg, 0.41 mmol),stirred at room temperature overnight, poured into water, extracted withEtOAc, dried (MgSO₄) and concentrated in vacuo. The crude product waspurified by chromatography [SiO₂; EtOAc:MeOH (1:10)] to give the titlecompound (26 mg, 14%) as a cream solid.

[0179] Method E

[0180]5-Amino-N-benzyl-7-(2Furyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidin-3-Ylcarboxamide(Example 10)

[0181] A solution of7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (202 mg, 1.0mmol) in DMF (3 mL) was treated with benzyl isocyanate (123 μL, 1.0mmol) and a catalytic amount of DMAP, stirred at room temperatureovernight, diluted with EtOAc and filtered to give the tide compound (62mg, 19%) as a peach coloured solid.

[0182] Method F

[0183] Ethyl5-Amino-7-(2-Furyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidin-3-Ylacetate(Example 14)

[0184] A solution of7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (101 mg, 0.5mmol) in DMF (4 mL) was treated with 4-(NN-dimethylamino)pyridine (5 mg,0.04 mmol) and ethyl bromoacetate (55 μL, 0.5 mmol), stirred at roomtemperature for 16 h and purified directly by chromatography [SiO₂;EtOAc:Heptane (1:2)] to give the title compound (50 mg, 35%) as a whitesolid.

[0185] Method G

[0186]7-2-Furyl)-3-(3-Hydroxybenzyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidine5-Amine(Example 18)

[0187] A solution of7-(2-furyl)-3-(3-methoxybenzyl)-3H-[1,²,³]triazolo[4,5-d]pyrimidine-5amine(119 mg, 0.37 mmol) in dichloromethane (20 mL) at 0° C. was treated withboron tribromide (1-M in dichloromethane, 8.8 mL, 8.8 mmol) portion-wiseover 3 days, concentrated in vacuo and isolated by filtration to givethe title compound (114 mg, 100%) as a yellow solid.

[0188] Method H

[0189] 6-(5-Methyl-2-Furyl)-5-Nitropyrimidine-2,4-Diamine

[0190] A solution of 6-chloro-5-nitropyrimidine-2,4-diamine (10 g, 60%pure, 32 mmol) in THF (300 mL) was treated with saturated aq NaHCO₃ (75mL), 5-methylfuran-2-boronic acid (7.33 g, 0.058 mol) and Pd(PPh₃)₄ (1g, 0.865 mmol) and refluxed with vigorous stirring under argonovernight. The mixture was cooled to room temperature, diluted withEtOAc (400 mL) and water (300 mL), filtered to remove insoluble materialand the filtrate was extracted with EtOAc (2×100 mL). The combinedorganic phase was dried (MgSO₄), concentrated in vacuo and the resultingsolid triturated with dichloromethane and filtered to give the titlecompound (6 g, 72%) as a yellow solid; mp 196.3-196.9° C.; IR ν_(max)(Nujol)/cm⁻⁴ 3442, 3169, 2930, 1629, 1463, 1377, 1027, and 790; NMRδ_(H) (400 MHz, DMSO) 7.40 (2H, br s), 7.09 (2H, br s), 6.87 (1H, dd, J0.5, 3.2 Hz), 6.26 (2H, dd, J 1.0, 3.3 Hz) and 2.28 (3H, s).

[0191] Method I

[0192] 6-(5-Methyl-2-Furyl)Pyrimidine-2,4,5-Triamine

[0193] A suspension of 6-(5-methyl-2-firyl)-5-nitroprdine-2,4-diamine(6.6 g, 29.6 mmol) and 10% Pd/C (0.66 g) in. MeOH (100 mL) was heated at40° C. under an atmosphere of H₂ for 3 h, cooled to room temperature,filtered through Celite, and concentrated in vacuo to give the titlecompound (5.8 g, 99%) as an off-white solid; IR ν_(max) (DR)/cm⁻¹ 3333,2237, 1634, 1458, 1237, 1025, 963 and 828; NMR δ_(H) (400 MIz, DMSO)6.77 (1H, dd, J 0.5, 3.2 Hz), 6.21-6.17 (3H, m), 5.14 (2H, s), 4.21 (2H,s), and 2.35 (3H, s).

[0194] Method J

[0195] 7-(5-Methyl-2-Furyl)-1H-[1,2,3]Triazolo[4,5-Dl]Primidine-5-Amine(Example 19)

[0196] A solution of 6-(5-methyl-2-furyl)pyrimidine-2,4,5-triarnine (5.8g, 30.1 mmol) in dioxane (116 mL) was treated with isoamyl nitrite (4.1mL, 30.5 mmol), heated at 80° C. for 3.5 h, cooled to room temperatureand the resulting precipitate was filtered, washed with dioxane (10 mL)and heptane (2×15 mL) then triturated with heptane and filtered to givethe title compound (4.7 g, 77%) as a sandy solid.

[0197] Method K

[0198] 7-(1H-Pyrazol-3-Yl)-1H-[1,2,3]Triazolo[4,5-D]Pyrimidine-5-Amine(Example 21)

[0199] A solution of7-(1-(2-(trimethylsilyl)ethoxymethyl)-1H-pyrazol-3-yl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(120 mg, 0.361 mmol) in MeOH (2 nmL) was treated with HC₁ (4-M indioxan, 1 mL), stirred for 2 h, filtered and the resulting solid washedwith Et₂O to give the title compound (76 mg, 100%) as a yellow solid.

[0200] Method L

[0201] (2-Amino-6-(2-Furyl)-5-Nitropyrinidin-4-Yl)4-Methylbenzenesulphonate

[0202] A suspension of 2-amino-6-(2-furyl)-5-nitropyrimidine4(1H)-one(1.00 g, 4.50 mmol) in dichloromethane (50 mL) was treated withtriethylamine (0.941 mL, 6.75 mmol) and p-toluenesulfonyl chloride (944mg, 4.95 mmol), stirred for 1 h, diluted with dichloromethane (50 mL),washed with 2-M HCl (20 mL), dried (MgSO₄), concentrated in vacuo andpurified by chromatography [SiO₂; isohexane:EtOAc (2:1)] to give thetitle compound (410 mg, 24%) as a yellow solid; NMR δ_(H) (400 Z, CDCl₃)7.95 (2H, d, J 8.5 Hz), 7.59-7.57 (1H, m), 7.39 (2H, d, J 8.5 Hz),7.23-7.21 (1H, m), 6.59-5.39 (2H, br s), 2.48 (3H, s); Retention time5.68 min.

[0203] Method M

[0204] 6-(2-Furyl)-5-Nitro-N4-(2-Pyridylmethyl)Pyrilidine-2,4-Diamine

[0205] A solution of (2-amino-6-(2-furyl)-5-nitropyrimidin-4-yl)4-methylbenzenesulphonate (478 mg, 1.27 mmol) in dimethoxyethane (15 mL)was treated with triethylarnine (0.531 mL, 3.81 mmol) and2-pyridinemethylamine (0.393 mL, 3.81 mmol), stirred for 16 h, pouredinto water (100 mL) and the resulting solid was filtered to give thetitle compound (275 mg, 69%) as a yellow solid; NMR δ_(H) (400 MHz,CDCl₃) 8.70-8.58 (2H, m), 7.70-7.66 (1H, m), 7.55-7.54 (1H, m), 7.28(1H, d, J 8.0 Hz), 7.24-7.20 (1H, m), 7.07-7.06 (1H, m), 6.54-6.52 (1H,m), 5.26 (2H, br s) and 4.83 (2H, d, J 5.0 Hz); Retention tim 1.44 min.

[0206] Method N

[0207]7-(2-Furyl)-3-(2-Pyridylmethyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrnidine-5-Amine(Example 24)

[0208] A solution of6-(2-frryl)-5-nitro-N⁴-(2-pyridylmethyl)pyrimidine-2,4diamine (270 mg,0.864 mmol) and 10% Pd/C (92 mg, 0.086 mmol) in EtOH (30 mL) and EtOAc(10 mL) was stirred under an hydrogen atmosphere for 1 h, filteredthrough Celite and concentrated in vacuo. The resulting yellow oil wasdissolved in in dioxane (25 mL), treated with isoamyl nitrite (0.109 mL,0.815 mmol), stirred at 100° C. for 6 h, cooled to room temperature,filtered through Celite, concentrated in vacuo and triturated with Et₂Oto give the title compound (110 mg, 46%) as a yellow solid.

[0209] Method O

[0210](5-Amino-7-(2-Furyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidin-3-Yl)Acetic Acid(Example 26)

[0211] A solution of ethyl5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylacetate (547mg, 1.89 mmol) in MeOH (5 mL) was treated with aqueous NaOH (2 mL, 2-M,4 rnmol), refluxed for 10 min, cooled, acidified with aqueous HCl (1-M),filtered and dried to give the title compound (417 mg, 85%) as a whitesolid.

[0212] Method P

[0213](5-Amino-7-(2-Furyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidin-3-Yl)-N-(3-Chlorophenyl)Acetamn(Example 31)

[0214] A suspension of(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)acetic acid(140 mg, 0.5 mmol) in DMP (1 mL) was treated with carbonyl dlimidazole(81 mg, 0.5 mmol), stirred at room temperature for 1 h, treated with3-chloroaniline (53 μL, 0.5 rnmol) and the mixture heated to 50° C. for16 h. The reaction mixture was cooled, diluted with water (3 mL) andfiltered to give the title compound (94 mg, 48%) as a cream solid.

[0215] Method Q

[0216]3-(2-Fluorobenzyl)-7-(2-Thiazolyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidine-5-Amine(Example 34)

[0217] A stirred solution of thiazole (0.10 mL, 1.43 mmol) in dry THEF(5 mL) at −78° C., under argon was treated with n-BuLi (0.9 mL, 1.6-M inhexanes, 1.43 mmol), stirred for 30 min, treated with a solution ofZnCl₂ (1.8 mL, 1-M in Et₂O, 1.80 mmol) and allowed to warm gradually toroom temperature. The mixture was treated with7-chloro-3-(2-fluorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(200 mg, 0.714 mmol) and Pd(PPh₃)₄ (50 mg), refluxed for 2 h andpartitioned between saturated NH₄Cl (20 mL) and EtOAc (20 mL). Theorganic phase was dried (MgSO₄), concentrated in vacuo and purified bychromatography [SiO₂; iso-hexane:EtOAc (1:1)) to give the title compound(70 mg, 30%) as a cream solid.

[0218] Method R

[0219]N-(2-Amino-6-(2-Furyl)-5-Nitropyrimidine-4-Yl)-6-Chloropyridine-3-Carboxainide

[0220] A solution of 6-(2-furyl)-5-nitropyrimidine-2,44diamnine (500 mg,2.26 mmol) in pyridine (10 mL) was treated with 6-chloronicotinoylchloride (438 mg, 2.49 mmol), stirred for 16 h at 80° C., cooled to roomtemperature, poured into water (100 mL) and extracted with EtOAc (2×25mL) and the combined organic phase was dried (MgSO₄), concentrated invacuo and purified by chromatography [SiO₂; isohexane:EtOAc (3:2)] togive the title compound (430 mg, 82%) as a yellow solid; NMR δ_(H) (400MH, DMSO) 11.14 (1H, s), 8.86 (1H, d, J 2.5 Hz), 8.27 (1H, dd, J 8.5,2.5 Hz), 7.93 (1H, m), 7.77 (2H, br s), 7.65 (1H, d, J 7.5 Hz), 7.09(1H, d, J 4.5 Hz), 6.72-6.70 (1H, m); Retention time 2.41 min.

[0221] Method T

[0222]6Chloro-N-(7-(2-Furyl)-1H,2,3]Triazolo[4,5-D]Pyrimidin-5-Yl)Pyridine-3-Carboxamide(Example 44)

[0223] A solution ofN-(2-amino-6-(2-frryl)-5-nitropyrimidine-4-yl)-6-chloropyridine-3-carboxamide(153 mg, 0.423 mmol) and 10% Pd/C (82 mg, 42.3 μmol) in EtOH (20 nal.)and EtOAc (5 mL) was stirred under an hydrogen atmosphere for 3 h,filtered through Celite and concentrated in vacuo to giveN-(2,5-diamino-6-(2-furyl)pyrimidin4-yl)-6-chloropyridine-3-carboxamideas a yellow oil. A solution of this product in EtOH (5 mL) and 2-M HCl(5 mL) at 0° C. was treated dropwise with an ice-cold solution of sodiumnitrite (87 mg, 1.27 mmol) in water (2 mL). The mixture was stirred at0° C. for 1 h, stirred at room temperature for 1 h, neutralised with 5-MNaOH, stirred for 16 h and the resulting solid was filtered to givetitle compound (40 mg, 28%) as a brown solid.

[0224] Method U

[0225] 6-Chloro-N-(3-Nitrobenzyl)Pyrimidine-2,4,5-Triamine

[0226] A mixture of 4,6-dichloropyrimidine-2,5-diamine (700 mg, 3.91mmol), 3-nitrobenzylamine hydrochloride (885 mg, 4.69 mmol) andtriethylamine (1.6 mL, 11.7 mmol) in n-BuOH (20 nmL) was refluxed for 17h, concentrated in vacuo and the residue partitioned between EtOAc (10mL) and H₂O (5 mL). The organic phase was dried (MgSO₄) and concentratedin vacuo to give the title compound as an orange solid (906 mg, 76%)which was used in the next reaction without further purification; NMRδ_(H) (400 MHz, CDCl₃) 8.16 (1H, s), 8.10 (1H, d, J 8.0 Hz), 7.80 (1H,d, J 7.5 Hz), 7.62 (1H, t, J 7.5 Hz), 7.25 (1H, t, J 6.0 Hz), 5.69 (2H,s), 4.67 (2H, d, J 6.0 Hz) and 3.93 (2H, br s).

[0227] Method V

[0228] 3-Chloromethyl-N,N-Dimethylbenzamide

[0229] A solution of 3-(chloromethyl)benzoyl chloride (426 μL, 3 rumol)and Et₃N (626 μL, 4.5 mmol) in THF (5 mL) was treated with dimethylamine(1.5 mL, 2-M in TBF, 3 mmol), stirred at room temperature for 1 h,poured into water, extracted with EtOAc, dried (MgSO₄) and concentratedin vacuo to give the title compound (580 mg, 98%) as a colourless oil;NMR δ_(H) (400 MHz, CDCl₃) 7.46-7.34 (4H, m), 4.59 (2H, s), 3H, s) and2.98 (3H, s); Anal. Calcd for C₁₂H₁₂N₆O₂•0.2 H₂O: C, 49.38; H, 4.28, N,28.79

[0230] Found: C, 49.25; H, 4.09; N, 28.47.

[0231] Method W

[0232]7-(2-Furyl)-3(2-Methoxy5-Nitrobenzyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidine-5-Amine(Example 66)

[0233] A solution of7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrmidine-5-amine (606 mg, 3 mmol)in DMF (5 mL) at 0° C., was treated with CsCO₃ (977 mg, 3 mrnol),stirred for 1 h, treated with 2-methoxy-5-nitrobenzyl bromide (738 mg, 3mmol) and stirred at room temperature for 1 h. The reaction mixture wasdiluted with water (10 mL), filtered and the resulting solid purified bychromatography [SiO₂; EtOAc:Heptane (2:1)] to give the title compound(279 mg, 25%) as a yellow solid.

[0234] Method X

[0235]3-(2-Fluorobenzyl)-7-(5-Oxazolyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidine-5-Amine(Example 69)

[0236] A stirred solution of oxazole (138 mg, 2.0 mmol) in dry TBF (10mL) at −78° C., under argon was treated with n-BuLi (1.25 mL, 1.6-M inhexanes, 2.0 mmol), stirred for 30 min, treated with a solution of ZnCl₂(2.0 mL, 1-M in Et₂O, 2.0 mmol)) and allowed to warm gradually to roomtemperature. The mixture was treated with7-chloro-3-(2-fluorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(280 mg, 1.0 mmol) and Pd(PPh₃)₄ (100 mg), refluxed for 4 h andpartitioned between saturated NH₄Cl solution (10 mL) and EtOAc (10 mL).The organic phase was dried (MgSO₄), concentrated in vacuo and purifiedby chromatography [SiO₂; iso-hexane:EtOAc (1:1), then neat EtOAc] togive the title compound (6 mg, 2%) as a beige solid.

[0237] Method Y

[0238]3-(2-Fluorobenzyl)-7-(1H-Triazol-4-Yl)-3H-[1,2,3]Triazolo[4,5-D]Pyriniie-5-Amine(Example 80)

[0239] A mixture of7-chloro-3-(2-fluorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(145 mg, 0.50 mmol), tributyl1-(2-(trimethylsilyl)ethoxymethyl)-1H-triazol-5-ylstannane (336 mg, 0.75mmol) and Pd(PPh₃)₂Ck₂ (35 mg, 0.05 mmol) in DMF (2 mL) was shaken at80° C. for 17 h then purified directly by chromatography [SiO₂;iso-hexane:EtOAc (2:1)] to give3-(2-fluorobenzyl)-7-(1-(2-trimethylsilyl)ethoxymethyl)-1H-triazol-5-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amineas a colourless oil. This material was dissolved in MeOH (1 mL), treatedwith a solution of HCl (0.5 mL, 4-M in dioxane), stirred for 17 h,concentrated in vacuo and the residue triturated with Et₂O to give thetitle compound (16 mg, 10%) as an off-white solid.

[0240] Method Z

[0241]3-(4-Hydroxylamino-2Pyridyhuethyl)7-(5-Methyl-2-Furyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidine-5-Amine(Example 87)

[0242] A solution of7-(5-methyl-2-furyl)-3-(4-nitro-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(60 mg, 0.17 mmol) in EtOH (40 mL), MeOH (20 mL) and water (15 mL) wastreated with ammonium chloride (280 mg, 5.23 mmol) and zinc (138 mg,2.05 miol), stirred for 1 h, filtered through Celite, concentrated invacuo to ˜20 mL, diluted with brine (20 mL), extracted with EtOAc (3×20mL) and the combined organic phase dried (MgSO₄) and concentrated invacuo to give the title compound (40 mg, 73%) as a yellow solid.

[0243] Method AA

[0244]3-(3-Aminomethylbenzyl)-7-(1H-Pyrazol-3-Yl)-3H-[1,2,3]Triazolo[4,5D]Pyrimidine5-Amine(Example 101)

[0245] A stirred solution of the7-(1-(2-(trimethylsilyl)ethoxymethyl)-1H-pyrazol-5-yl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(330 mg, 1 mmol) in dry DMF (5 mL) was treated with NaH (40 mg, 60% inoil, 1 mmol), stirred for 15 min, treated with tert-butylN-(3-(bromomethyl)benzyl)carbamate (300 mg, 1 mmol) and stirred for 1 h.The mixture was partitioned between EtOAc (20 mL) and H₂O (20 mL), theorganic phase was dried (MgSO₄), concentrated in vacuo and purified bychromatography [SiO₂; iso-hexane:EtOAc (1:1)]. The resulting yellowsyrup was dissolved in MeOH (3 mL), treated with HCl (2 mL, 4M indioxane), stired for 17 h and the resulting solid filtered to give thetitle compound (258 mg, 80%) as a cream solid.

[0246] Method AB

[0247] 2-Bromomethyl-6-(Methoxymethyl)Pyridine

[0248] A solution of 6-methoxymethyl-2-pyridinemethanol (860 mg, 5.64mmol) and triphenylphosphine (1.78 g, 6.77 mmol) in dichloromethane (40mL) at 0° C. was treated portion wise with CBr₄ (2.80 g, 8.43 mmol),stirred for 1. h, concentrated in vacuo and purified by chromatography[SiO₂; isohexane:EtOAc (3:1)] to give the title compound (1.20 g, 99%)as a colourless oil; NMR δ_(H) (400 MHz, CDCl₃) 7.71 (1H, t, J 8.0 Hz),7.35 (2H, d, J 8.0 Hz), 4.58 (2H, s) and 4.54 (2H, s).

[0249] The following novel compounds were also synthesised by Method ABfrom the appropriate alcohol.

[0250] 2-Bromomethyl-4-Methylpyridine

[0251] NMR δ_(H) (400 MHz, CDCl₃) 8.43 (1H, d, J 5.0 Hz), 7.26-7.25 (1H,m), 7.03 (1H, d, J 5.0 Hz), 4.51 (2H, s) and 2.36 (3H, s).

[0252] 2-Bromomethyl-6-Ethylpyridine

[0253] NMR δ_(H) (400 z, CDCl₃) 7.60 (1H, t, J 7.5 Hz), 7.26 (1H, d, J7.5 Hz), 7.08 (1H, d, J 7.5 Hz), 4.53 (2H, s), 2.82 (2H, q, J 7.5 Hz)and 1.30 (3H, t, J 7.5 Hz).

[0254] 4-Bromomethyl-2-Ethylpyridine

[0255] NMR δ_(H) (400 MHz, CDCl₃) 8.51 (1H, d, J 5.0-Hz), 7.17-7.16 (1H,m), 7.13-7.11 (1H, m), 4.37 (2H, s), 2.84 (2H, q, J 7.5 Hz) and 1.32(3H, t, J 7.5 Hz).

[0256] Tert-Butyl (4-Bromomethyl-3,5-Difluorophenyl) Carbonate

[0257] NMR δ_(H) (400 MHz, CDCl₃) 6.80 (2H, m), 4.49 (2H, s) and 1.56(91H, s).

[0258] 2-Fluoro-5-Iodobenzyl Bromide

[0259] NMR δ_(H) (400 MHz, DMSO) 7.94-7.91 (1H, dd, J2.5, 7.5 Hz),7.76-7.71 (1H, m), 7.12-7.06 (1H, dd, J 8.5, 10.0 Hz) and 4.66-4.64 (2H,s).

[0260] 2-Allyloxymethyl-6-Bromomethylpyridine

[0261] NMR δ_(H) (400 MHz, CDCl₃) 7.71 (1H, t, J 7.5 Hz), 7.40 (1H, d, J7.5 Hz), 7.34 (1H, d, J 7.5 Hz), 6.03-5.93 (111, m), 5.37-5.32 (1H, m),5.26-5.22 (1H, m), 4.64 (2H, s), 4.54 (2H, s) and 4.14-4.12 (2H1, m).

[0262] 4-Nitro2-(2-Trimethylsflylethoxy)Methoxybenzyl Br Mide

[0263] NMR δ_(H) (400 z, CDCl₃) 7.99 (1H, d, J 2.0 Hz), 7.84 (1H, dd, J8.4, 2.0 Hz), 7.49 (1H, d, J 8.4 Hz), 5.41 (2H, s), 4.55 (2H, s), 3.82(2H, m), 0.96 (2H, m) and 0.01 (9H, s).

[0264] 2-Bromomethyl-4,6-Diisopropylpyridine

[0265] NMR δ_(H) (400 MHz, CDCl₃) 7.12 (1H, s), 6.93 (1H, s), 4.52 (2H,s), 3.03 (1H, sept. J 7.0 Hz), 2.87 (1H, sept, J 7.0 Hz), 1.29 (6H, d, J7.0 Hz) and 1.25 (6H, d, J 7.0 Hz).

[0266] 2-Bromomethyl-6-Isopropylpyridine

[0267] NMR δ_(H) (400 MHz, CDCl₃) 7.63-7.59 (1H, m), 7.27-7.25 (1H, m),7.10-7.08 (1H, m), 4.54 (2H, s), 3.06 (1H, sept, J 7.0 Hz) and 1.30 (6H,d, J 7.0 Hz).

[0268] 2-Bromomethyl-6-Vinylpyridine

[0269] NMR δ_(H) (400 MHz, CDCl₃) 7.66 (1H, t, J 7.5 Hz), 7.34-7.28 (2H,m), 6.81 (bH, dd, J 10.5, 17.5 Hz), 6.22 (1H, dd, J 1.0, 17.5 Hz), 5.51(1H, dd, J 1.0, 10.5 Hz) and 4.55 (2H, s).

[0270] 2-Bromomethyl-5-Ethylthiophene

[0271] NMR δ_(H) (400 MHz, DMSO) 6.85-6.82 (1X, d, J 3.5 Hz), 6.71-6.68(1H, d, J 3.5 Hz), 4.59-4.55 (2H, s), 2.81-2.75 (2H, m) and 1.25-1.20(3H, m).

[0272] 2-Bromomethyl-6-N-Propylpyridine

[0273] NMR δ_(H) (400 MHz, CDCl₃) 7.59 (1H, t, J 7.5 Hz), 7.26 (1H, d, J7.5 Hz), 7.06 (1H, d, J 7.5 Hz), 4.53 (211, s), 2.76 (2H, t, J 7.5 Hz),1.74 (2H, t, J 7.5 Hz) and 0.97 (3H, t, J 7.5 Hz).

[0274] 2-Bromomethyl-6-Isobutyloxymethylpyridine

[0275] NMR δ_(H) (400 MHz, CDCl₃) 7.71 (1H, t, J 7.5 Hz), 7.41 (1H, d, J7.5 Hz), 7.33 (1H, d, J 7.5 Hz), 4.62 (2H1, s), 4.53 (2H, s), 3.33 (2H,d, J 6.5 Hz), 1.91-2.01 (1H, m) and 0.96 (6H, d, J 6.5 Hz).

[0276] 5-Bromomethyl-2-Isopropylpyridine

[0277] NMR δ_(H) (400 MHz, CDCl₃) 8.54 (1H, m), 7.65 (1H, dd, J 2.5, 8.0Hz), 7.16 (1H, d, J 8.0 Hz), 4.47 (2H, s), 3.07 (1H, sept, J 7.0 Hz) and1.30 (6X, d, J 7.0 Hz).

[0278] 2-Bromomethyl-6-Isobutyloxymethylpyridine

[0279] NMR δ_(H) (400 MHz, CDCl₃) 7.71-7.67 (1H, m), 7.42-7.40 (1H, m),7.33-7.31 (1H, m), 4.63 (2H, S), 4.53 (2H, s), 3.75 (1H, sept, J 6.0 Hz)and 1.25 (6H, d, J 6.0 Hz).

[0280] Method AC

[0281] 2-Bromomethyl-4-Nitropyridine

[0282] A solution of 2-methylnitropyridine (1.79 g, 13.0 mmol) in CC₁₄(30 mL) was treated with N-bromosuccinimide (2.31 g, 13.0 mmol) andbenzoyl peroxide (420 mg, 1.30 mmol), stirred at 80° C. for 16 h, cooledto room temperature, filtered through Celite, concentrated in vacuo andpurified by chromatography [SiO₂; isohexane:EtOAc (15:1)] to give thetitle compound (700 mg, 25%) as a colourless oil; NMR 8H (400 IKL,CDCl₃) 8.89 (1H, d, J 5.0 Hz), 8.19 (1H, d, J 2.0 Hz), 7.96 (1H, dd, J5.0, 2.0 Hz) and 4.66 (2H, s).

[0283] The following novel compounds were also synthesised bybromination of the appropriate arylalkyl compounds using Method AC.

[0284] 2-Bromomethyl-6-Methyl-4-Nitropyridine

[0285] NMR δ_(H) (400 MHz, CDCl₃) 7.99-7.98 (1H, m), 7.79 (1H, d, J 2.0Hz), 4.60 (2H, s) and 2.71 (3H, s).

[0286] Tert-Butyl 7-Bromomethylindole-1-Carboxylate

[0287] NMR δ_(H) (400 MHz, CDCl₃) 7.57 (1H, d, J 4.0 Hz), 7.55 (1H, dd,J 8.0, 1.5 Hz), 7.27 (1H, d, J 7.5 Hz), 7.19 (1H, t, J 7.5 Hz), 6.58(1H, d, J 3.5 Hz), 5.24 (2H, s) and 1.68 (9H, s).

[0288] Tert-Butyl 5-Bromomethylindole-1-Carboxylate

[0289] NMR δ_(H) (400 MHz, CDCl₃) 8.11 (1H, br d, J 8.5 Hz), 6.72 (1H,d, J 3.5 Hz), 7.59 (1H, d, J 1.5 Hz), 7.35 (1H, dd, J 8.5, 1.5 Hz), 6.54(1H, d, J 4.0 Hz), 4.64 (2H, s) and 1.67 (9H, s).

[0290] Tert-Butyl 7-Bromomethyl-5-Chloroindole-1-Carboxylate

[0291] NMR δ_(H) (400 MHz, CDCl₃) 7.58 (1H, d, J 3.5 Hz), 7.51 (1H, d, J2.0 Hz), 7.27 (1H, m), 6.52 (1H, d, J3.5 Hz), 5.15 (2H, s), and 1.67(9H, s).

[0292] Tert-Butyl 7-Bromomethyl-5-Methylindole-1-Carboxylate

[0293] NMR δ_(H) (400 MHz, CDCl₃) 7.53 (1H, d, J 4.0 Hz), 7.32 (1H, s),7.09 (1H, s), 6.49 (1H, d, J 3.5 Hz), 5.21 (2H, s), 2.41 (3H, s) and1.66 (9H, s).

[0294] Tert-Butyl 5-Bromomethyl-7-Fluoroindole-1-Carboxylate

[0295] NMR δ_(H) (CDCl₃) 7.65 (1H, d, J 4.0 Hz), 7.35 (1H, d, J 1.5 Hz),7.07 (1H, dd, J 13.0, 1.5 Hz), 6.56 (1H, dd, J 3.5, 1.5 Hz), 4.56 (2H,s) and 1.65 (9H, s).

[0296] Tert-Butyl 5-Bromomethyl-4-Chloroindole-1-Carboxylate

[0297] NMR δ_(H) (400 MHz, CDCl₃) 8.03 (1H, d, J 8.5 Hz), 7.63 (1H, d, J4.0 Hz), 7.36 (1H, d, 8.5 Hz), 6.71 (1H, d, J 3.5 Hz), 4.75 (2H, s) and1.67 (9H, s).

[0298] Tert-Butyl 7-Bromo-5-Bromomethylindole-1-Carboxylate

[0299] NMR δ_(H) (400 MHz, CDCl₃) 7.57 (1H, s), 7.56-7.52 (2H, m), 6.54(1H, d, J 3.5 Hz), 4.56 (2H, s) and 1.66 (9H, s).

[0300] Tert-Butyl 5-Bromomethyl-6-Chloroindolel-Carboxylate

[0301] NMR δ_(H) (400 MHz, CDCl₃) 8.23 (1H, br s), 7.60 (1H, s), 7.58(1H, d, J 3.5 Hz), 6.51 (1H, d, J4.5 Hz), 4.71 (2H, s) and 1.67 (9H, s).

[0302] Tert-Butyl 5-Bromomethyl-6-Fluoroindole-1-Carboxylate

[0303] NMR δ_(H) (400 MHz, CDCl₃) 7.88 (1H, br, d, J 11.0 Hz), 7.57 (1H,d, J 4.0 Hz), 7.54 (1H, d, J 7.0 Hz), 6.52 (1H, d, J 4.5 Hz), 4.64 (2H,s) and 1.67 (9H, s).

[0304] Tert-Butyl 2-Bromomethyl-5-Fluoroindole-1-Carboxylate

[0305] NMR δ_(H) (400 MHz, CDCl₃) 8.12 (1H, dd, J 9.0, 4.5 Hz), 7.15(1H, dd, J 8.5, 2.5 Hz), 7.04 (1H, dt, J 9.0, 2.5 Hz), 6.66 (1H, s),4.90 (2H, s) and 1.72 (9H, s).

[0306] Tert-Butyl 5-Bromomethyl-7-Chloroindole-1-Carboxylate

[0307] NMR δ_(H) (400 MHz, CDCl₃) 7.56 (1H, d, J 4.0 Hz), 7.49 (1H, d, J2.0 Hz), 7.37 (1H, s), 6.54 (1H, d, J 3.5 Hz), 4.56 (2H, s) and 1.65(9H, s).

[0308] 2-(1-Bromopropyl)-5,6-Dimethylpyridine

[0309] NMR δ_(H) (400 MHz, CDCl₃) 7.39 (1H, d, J 8.0 Hz), 7.18 (1H, d, J8.0 Hz), 4.93 (1H, t, J 7.5 Hz), 2.49 (3H, s), 2.27 (3H, s), 2.29-2.24(2H, m) and 1.02 (3H, t, J 7.0 Hz); MIZ 228 (M+H)⁺.

[0310] The following novel compound was synthesised by bromination of2-(1-methoxypropyl)-6-methylpyridine using Method AC.

[0311] 2-Bromo-1-(6-Methylpyridin-2-Yl)Propanone

[0312] NMR δ_(H) (400 MHz, CDCl₃) 7.91 (1H, d, J 7.5 Hz), 7.74 (1H, t, J7.5 Hz), 7.35 (1H, d, J 7.5 Hz), 6.13 (1H, q, J7.0 Hz), 2.62 (3H, s) and1.89 (3H, d, J7.0 Hz).

[0313] Method AD

[0314] Tert-Butyl 7-Methylindole-1-Carboxylate

[0315] A stirred solution of 7-methylindole (1.18g, 9 mmol) in dry ThF(50 mL) was treated with NaH (360 mg, 60% in oil, 9 mmol), stirred for10 min, treated with di-tert-butyl dicarbonate (2.3 mL, 9.3 mmol),stirred for 1 h, treated with 4-(N,N-dimethylamino)pyridine (catalyticamount) and stirred for 1 h. The mixture was partitioned between EtOAc(50 mL) and saturated NH₄Cl solution (30 mL) and the organic phase wasdried (MgSO₄), concentrated in vacuo, and purified by chromatography[SiO₂; iso-hexane:EtOAc (5:1)] to give the title compound (2.35 g, 100%)as an orange oil; NMR δ_(H) (400 MHz, CDCl₃) 7.51 (1H, d, J 4.0 Hz),7.37 (1H, d, J 7.5 Hz), 7.13 (1H, t, J 7.5 Hz), 7.08 (1H, d, 7.5 Hz),6.51 (1H, d, J 4.0 Hz), 2.64 (3H, s) and 1.63 (9H, s).

[0316] The following novel compounds were synthesised from theappropriate indoles using Method AD.

[0317] Tert-Butyl 5-Chloro-7-Methylindole-1-Carboxylate

[0318] NMR δ_(H) (400 MHz, CDCl₃) 7.52 (1H, d, J 4.0 Hz), 7.35 (1H, d, J2.0 Hz), 7.07 (1H, d, J 1.5 Hz), 6.46 (1H, d, J 3.5 Hz), 2.61 (3H, s),and 1.63 (9H, s).

[0319] Tert-Butyl 5,7-Dinethylind Le-1-Carboxylate

[0320] NMR δ_(H) (CDCl₃) 7.48 (1H, d, J 4.0 Hz) 7.16 (1H, s), 6.92 (1H,s), 6.44 (1H, d, J 4.0 Hz), 2.60 (3H, s) 2.38 (3H, s) and 1.62 (9H, s).

[0321] Tert-Butyl 7-Fluoro-5-Methylindole-1-Carboxylate

[0322] NMR δ_(H) (CDCl₃) 7.59 (1H, d, J4.0 Hz), 7.10 (IH, s), 6.84 (1H,d, J 13.5 Hz), 6.50-6.47 (1H, m), 2.40 (3H, s) and 1.64 (9H, s).

[0323] Tert-Butyl 4-Chloro-5-Methylindole-1-Carboxylate

[0324] NMR δ_(H) (400 MHz, CDCl₃) 7.92 (1H, d, J 8.0 Hz), 7.57 (1H, d, J3.5 Hz), 7.15 (1H, d, J 8.5 Hz), 6.66 (1H, d, J 3.5 Hz), 2.46 (3H, s)and 1.66 (9H₁ s).

[0325] Tert-Butyl 7-Bromo-5-Methylindole-1-Carboxylate

[0326] NMR δ_(H) (400 MHz, CDCl₃) 7.47 (1H, d, J 3.5 Hz), 7.35 (1H, s),7.26 (1H, s), 6.44 (1H, d, J4.0 Hz), 2.38 (3H, s) and 1.64 (9H, s).

[0327] Tert-Butyl 6-Chloro-5-Methylindole-1-Carboxylate

[0328] NMR δ_(H) (400 MHz, CDCl₃) 8.17 (1H, br s), 7.53 (1H, d, J 3.5Hz), 7.38 (1H, s), 6.46 (1H, d, J 3.0 Hz), 2.44 (3H, s), 1.67 (9H, s).

[0329] Tert-Butyl 6-Fluoro-5-Methylindole-1-Carboxylate

[0330] NMR δ_(H) (400 MHz, CDCl₃) 7.79 (1H, br d, J 10.5 Hz), 7.51 (1H,d, J 3.5 Hz), 7.30 (1H, d, J 7.5 Hz), 6.46 (1H, d, J 3.5 Hz), 2.34 (3H,s) and 1.66 (9H, s).

[0331] Tert-Butyl 5-Fluoro-2-Methylindole-1-Carboxylate

[0332] NMR δ_(H) (400 MHz, CDCl₃) 8.04 (1H, dd, J 9.0, 4.5 Hz), 7.07(1H, dd J 9.0, 2.5 Hz), 6.92 (1H, dt, J 9.5, 3.0 Hz), 6.27 (1H, s), 2.58(3H, d, J 1.5 Hz) and 1.67 (9H, s).

[0333] Tert-Butyl 7-Chloro-5-Methylindole-1-Carboxylate

[0334] NMR δ_(H) (400 MHz, CDCl₃) 7.50 (1H, d, J 3.5 Hz), 7.22 (1H, s),7.14 (1H, s), 6.46 (1H, d, J 4.0 Hz), 2.38 (3H, s) and 1.64 (9H, s).

[0335] The following novel compound was synthesised from2,6-difluoro-4-hydroxybenzyl alcohol using Method AD.

[0336] Tert-Butyl (3,5-Difluoro-4-Hydroxymethylphenyl) Carbonate

[0337] IR ν_(max) (DR)/cm⁻¹ 3388, 2983, 1775, 1605, 1446, 1396, 1373,1289, 1146, 1072, 967 and 882; NMR δ_(H) (400 MHz, CDCl₃) 6.79 (2H, m),4.75 (2H, d, J 6.5 Hz), 1.84 (1H, t, J 6.5 Hz) and 1.56 (9H, s).

[0338] Method AE

[0339] 2,6-Difluoro-4-Hydroxybenzyl Alcohol

[0340] A mixture of 3,5difluorophenol (25 g, 0.19 mol) and KOH (85%,12.7 g, 0.19 mol) was treated dropwise with water (50 mL), stirred at60° C. for 1 h, treated dropwise with formaldehyde solution (37%, 15.6mL, 0.19 mol) and water (50 mL) and stirred overnight at 40° C. Themixture was cooled, acidified with 6-M HCl, filtered and the resultingsolid washed with water and dried to give the title compound (15 g, 49%)as a white solid: NMR δ_(H) (400 MHz, DMSO) 10.28 (1H, s), 6.43 (2H, m),4.99 (1H, t, J 5.6 Hz) and 4.37 (2H,d,J5.6Hz).

[0341] Method AF

[0342]7-(2-Furyl)-3-(6-Indolylmethyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidine-5-Amine(Example 152)

[0343] A mixture of tert-butyl6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-yl (135 mg,4.08 mmol), and NaOMe (22 mg, 4.08 mmol) in MeOH (10 mL) was refluxedfor 1 h, treated with NaOMe (110 mg, 20.4 mmol), refluxed for a further4 h then stirred at room temperature for 17 h. The mixture wasconcentrated in vacuo to half volume and the resulting precipitate wasfiltered and washed with H₂O to give the title compound (90 mg, 96%) asa cream solid.

[0344] Method AG

[0345]3-(2,6-Difluoro-4-Methoxybeny)-7-(2-Furyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidine-5-Amine(Example 156)

[0346] A solution of3-(2,6-difluoro-4-hydroxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-aminehydrochloride (130 mg, 0.34 mmol) in DUF (5 mL) at 0° C., was treatedwith CsCO₃ (223 mg, 0.68 nmmol), stirred for 10 min, treated with methyliodide (21 μL, 0.34 mmol) and stirred at room temperature for 30 min.The reaction mixture was diluted with water (10 mL) and filtered to givethe title compound (122 mg, 100%) as a white solid.

[0347] Method AH

[0348] 2-Fluoro-5-Iodobenzyl Alcohol

[0349] A solution of 2-fluoro-5-iodobenzaldehyde (1.173 g, 4.692 mmol)in isopropanol (25 mL) was treated with sodium borohydride (0.379 g,10.02 mmol), stirred at room temperature for 18 h, poured into water(125 mL), and extracted with isopropyl ether (2×25 mL). The combinedorganic phase was dried (Na₂SO₄), and concentrated in vacuo to give thetitle compound (1.187 g, 99%) as a pale yellow solid; NMR δ_(H) (400MHz, CDCl₃) 7.77 (1H, m), 7.57 (1H, m), 6.82 (1H, t, J 8.8 Hz), 4.73(2H, d, J 6.1 Hz), and 1.79 (1H, t, J 6.1 Hz).

[0350] Method AI

[0351] 3-(Tert-Butoxycarbonyloxy)-4-Nitrobenzoic Acid

[0352] A solution of 3-hydroxy4nitrobenzoic acid (1.83 g, 10 mmol) inTHF (10 mL) was treated with Et3N (3.4 mL, 24 mmol) and di-tert-butyldicarbonate (2.40 mL, 11 mmol) and stirred at room temperature for 16 h.The reaction mixture was poured into 10% citric acid solution (20 mL),extracted with EtOAc (2 x 10 mL), dried (MgSO₄) and concentrated invacuo to give the title compound (2.36 g, 83%) as a cream solid; IRν_(max) (Nujol)/cm⁻¹ 2985, 1772, 1717 and 1592; NMR δ_(H) (400 MHz,DMSO) 13.85 (1H, s), 8.26 (1H, d, J 8.5 Hz), 8.04 (1H, dd, J 8.5, 2.0Hz), 7.98 (1H, d, J 2.0 Hz) and 1.49 (9H, s).

[0353] Method AJ

[0354] Tert-Butyl (5-Bromomethyl-2-Nitrophenyl) Carbonate

[0355] A solution of 3-(tert-butoxycarbonyloxy)Anitrobenzoic acid (2.26g, 8 mmol) and N-methylmorpholine (1.85 mL, 16.8 mmol) in THP (20 mL) at0° C., was treated with isobutylchloroformate (1.09 mL, 8.4 mmol) andstirred for l h. The reaction mixture was added to a cooled (−78° C.)solution of NABIL (605 mg, 16 mmol) in MeOH (16 nmL) and stirred at roomtemperature for 1 h. The reaction mixture was diluted with EtOAc (20mL), washed with saturated NaHCO₃ (10 mL) and 10% citric acid solution(10 mL), dried (MgSO₄) and concentrated in vacuo to give tert-butyl(5-hydroxymethyl-2-nitrophenyl) carbonate (1.36 g, 86%) as a creamsolid. This material was brominated directly using Method AB to give thetitle compound (961 mg, 58%) as a yellow oil: NMR δ_(H) (400 MHz, CDCl3)8.09 (1H, d, J 8.4 Hz), 7.41 (1H, dd, J 8.4, 2.0 Hz), 7.34 (1H, d, J 2.0Hz), 4.47 (2H, s) and 1.58 (9H, s).

[0356] Method AK

[0357]3-(3-Nitrobenzyl)-7-(1H-Pyrazol-3-Yl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidine-5-AmineHydrochloride (Example 266)

[0358] A soluition of7-chloro-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(306 mg, 1 mmol),1-(2-(trimethylsilyl)ethoxymethyl)-1H-pyrazol-5-ylboronic acid (2 mmol),Pd(PPh₃)₄ (100 mg) and saturated NaHCO₃ (5 mL) in THF (20 mL) wasrefluxed for 2 h, diluted with water (20 mL), extracted with EtOAc(2 x20 mL), dried (MgSO₄), concentrated in vacuo and purified bychromatography [SiO₂; CH₂Cl₂ :EtOAc (6:1)] to give3-(3-nitrobenzyl)-7-(1-(2-(trimethylsilyl)ethoxymethyl)-1H-pyrazol-5-yl)-3-H[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(156 mg, 34%) as a pale yellow syrup.

[0359] A solution of3-(3-nitrobenzyl)-7-(1-(2-(trimethylsilyl)ethoxymethyl)-1H-pyrazol-5-yl)3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(156 mg, 0.34 mmol) in MeOH (2 mTL) was treated with 4-M HCl in dioxane(4 mL) stirred at room temperature for 2 h, concentrated in vacuo,triturated with Et20 and filtered to give the title compound (110 mg,97%) as a yellow solid.

[0360] Method AL

[0361]3-(6-Acetamidomethyl-2-Pyridylmethyl)-7-(2-Furyl)-3H-[1,2,3]Triazolo[4,5D]Pyrimidine-5-Amine(Example 177)

[0362] A suspension of7-(2-furyl)-3-(6-phthalimidomethyl-2-pyridylmethyl)-3-H[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(210 mg, 0.465 mmol) in EtOH (50 mL) was treated with ethylenediamine(62 μl, 0.929 mmol), stirred for 3 h at 90° C. and the resulting clearsolution, cooled to room temperature and concentrated in vacuo to give3-(6aminomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine.A solution of this material in pyridine (10 mL) at 0° C. was treatedwith acetyl chloride (109 ml, 1.53 mmol), stirred for 10 min, pouredinto water (70 mL), extracted with EtOAc (3×20 mL) and the combinedorganic phase was dried (MgSO₄), concentrated in vacuo and purified bychromatography [SiO₂; EtOAc] to give the title compound (110 mg, 65%) asa beige solid.

[0363] Method AM

[0364]3-(6-Allyloxymethyl-2-Pyridylmethyl)-N,N-Diallyl-7-(2-Furyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidine-5-Amine(Example 182)

[0365] A solution of7-(2-furyl)-3-(6-hydroxymethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(120 mg, 0.377 mmol) in DMF (5 mL) at 0° C. was treated with sodiumhydride (30 mg, 0.743 mmol), stirred for 15 min, treated with allylbromide (96 μl, 1.11 mmol), stirred at room temperature for 16 h,concentrated in vacuo to ˜2 mL and purified by chromatography [SiO₂;isohexane:EtOAc (3:1)] to give the title compound (50 mg, 30%) as ayellow solid.

[0366] Method AN

[0367] 6-Allyloxymethyl-2-Pyridinemethanol

[0368] A solution of 2,6-pyridinedimethanol (5.0 g, 35.9 mmol) in DMP(30 mL) at 0° C. was treated with sodium hydride (1.44 g, 35.9 mmol),stirred for 30 min, treated with allyl bromide (3.42 ml, 39.5 mmol),stirred for 16 h at room temperature, poured into water (150 mL),extracted with EtOAc (3×30 mL) and the combined organic phase was dried(MgSO₄), concentrated in vacuo and purified by chromatography [SiO₂;isohexane:EtOAc (3:1 to 1:1)] to give the title compound (1.56 g, 24%)as a colourless oil: NMR δ_(H) (400 MD, CDCl₃) 7.69 (1H, t, J 7.5 Hz),7.37 (1H, d, J 7.5 Hz), 7.13 (1H, d, J 7.5 Hz), 6.04-5.93 (1H, m),5.38-5.21 (2H, m), 4.74 (2H, d, J 5.0 Hz), 4.65 (2H, s), 4.15-4.09 (2H,m) and 3.76 (1H, t, J 5.0 Hz).

[0369] The following novel compounds were synthesised from theappropriate alcohols by Method AN

[0370] 2-(1-Methoxypropyl)-6-Methylpyridine

[0371] NMR δ_(H) (400 MHz, CDCl₃) 7.58 (1H, t, J 8.0 Hz), 7.18 (1H, d, J8.0 Hz), 7.04 (1H, d, J 8.0 Hz), 4.17 (1H, dd, J 5.5, 7.5 Hz), 3.30 (3H,s), 2.55 (3H, s), 1.84-1.69 (2H, m) and 0.93 (3H, t, J 7.5 Hz).

[0372] 6-Isobutyloxymethylpyridine-2-Methanol

[0373] NMR δ_(H) (400 MHz, CDCl₃) 7.69 (1H, t, J 7.5 Hz), 7.37 (1H, d, J7.5 Hz), 7.13 (1H, d, J 7.5 Hz), 4.74 (2H, s), 4.63 (2H, s), 3.94 (1H,br s), 3.33 (2H, d, J 6.5 Hz), 1.91-2.01 (1H, m) and 0.96 (6H, d, J 6.5Hz).

[0374] 6-Isobutyloxymethylpyridine-2-Methanol

[0375] NMR δ_(H) (400 MHz, CDCl₃) 7.70-7.66 (1H, m), 7.39 (1H, d, J 7.5Hz), 7.11 (1H, d, J 8.0 Hz), 4.74 (2H, s), 4.64 (2H, s), 3.75 (1H, sept,J 6.0 Hz) and 1.25 (6H, d, J 6.0 Hz).

[0376] Method AO

[0377] 3-Isopropyl-4-Nitrobenzyl Bromide

[0378] A solution of 4-nitrobenzyl bromide (432 mg, 2 mmol) in ThF (5mL) at −70° C., was treated dropwise with isopropylmagnesium chloride (1mL, 2-M in Et₂O, 2 mmol), stirred for 1 h, treated with DDQ (499 mg, 2.2mmol) and stirred at room temperature for 16 h. The reaction mixture waspoured into water (10 mL), extracted with EtOAc (2×10 mL), dried(MgSO₄), concentrated in vacuo and filtered. The resulting solid waspurified by chromatography [SiO₂; EtOAc:Heptane (1:4)] to give the titlecompound (183 mg, 35%) as a pale yellow solid which was used in the nextreaction without further purification.

[0379] The following novel compound was also synthesised from4-nitrobenzyl bromide using Method AO

[0380] 3-Ethyl-4-Nitrobenzyl Bromide

[0381] NMR δ_(H) (400 MHz, CDCl₃) 7.87 (1H, d, J 8.3 Hz), 7.37 (1H, s),7.35 (1H, d, J 8.3 Hz), 4.47 (2H, s), 2.92 (2H, q, J 7.5 Hz) and 1.30(3H, t, J 7.5 Hz).

[0382] Method AP

[0383] 2-(Trimethylsilyl)Ethoxymethyl4-Nitro-2-((2-Trimethylsilyl)Ethoxymethoxy)Benzoic Acid

[0384] A solution of 2-hydroxy-4-nitrobenzoic acid (1.83 g, 10 mmol) inTPF (20 mL), was treated with NN-diisopropylethylamine (3.92 mL, 22mmol) and 2-(trimethylsilyl)ethoxymethyl chloride (3.46 mL, 20 mmol) andstirred for 16 h then purified directly by chromatography[SiO₂:EtOAc:heptane (1:4)] to give the title compound (5.82 mg,quantitative) as white solid which was used in the next reaction withoutfurther purification; NMR δ_(H) (400 MHz, CDCl₃) 8.09-8.07 (1H, m),7.87-7.85 (2H, m), 5.50 (2H, s), 5.35 (2H, s), 3.78 (4H, t, J 8.5 Hz),1.00-0.88 (4H, m), 0.00 (9H, s) and 0.03 (9H, s).

[0385] Method AQ

[0386] 2-(2-Trimethylsilyl)Ethoxymethoxy-4-Nitrobenzyl Alcohol

[0387] A solution of 2-(trimethylsilyl)ethoxymethyl4-nitro-2-(2-(trimethylsilyl)ethoxymethoxy)benzoic acid (2.91 mg, 5mmol) in Et₂O (10 mL) at 0° C., was treated with LiAIH₄ (190 mg, 22mmol) and stirred for 30 min. The reaction mixture was poured into water(20 mL), extracted with EtOAc (2×10 mL), dried (MgSO₄) and concentratedin vacuo to give the title compound (1.35 g, 91%) as a slightly impurecolourless oil; NMR δ_(H) (400 MHz, CDCl₃) 7.96-7.99 (1H, m), 7.90 (1H,dd, J 8.5, 2.0 Hz), 7.55 (1H, d, J 8.5 Hz), 5.35 (2H, s), 4.78 (2H, s),3.80-3.74 (2H, m), 0.99-0.94 (2H, m) and 0.00 (9H, s).

[0388] Method AR

[0389] 4,6-Diisopropyl-2-Pyridinemethanol

[0390] A solution of 2-pyridinemethanol (5.00 g, 45.8 mmol), conc.sulfuric acid (2.44 ml, 45.8 mmol), iron(II) sulfate heptahydrate (1.53g, 5.50 mmol) and isopropyl iodide (13.7 ml, 137 mmol) in DMSO (150 mL)was treated dropwise with hydrogen peroxide (27.5wt% in H₂0, 17.0 mL,137 mmol), with ice-bath cooling to maintain the internal temperature at25-30° C. A further portion of iron(II) sulfate heptahydrate (1.53 g,5.50 mmol) was added, the mixture was allowed to cool to roomtemperature over 1 h, poured into water (500 mL), basified to pH 9 with5-M NaOH, extracted with dichloromethane (3×100 mL) and the combinedorganic phase was dried (MgSO₄), concentrated in vacuo and purified bychromatography [SiO₂; isohexane:EtOAc (3:2)] to give4,6-diisopropyl-2-pyridinemethanol (500 mg, 6%) as a colourless oil; NMRδ_(H) (400 MHz, CDCl₃) 6.90 (1H, s), 6.85 (1H, s), 4.69 (2H, br s), 4.35(1H, br s), 3.03 (1H, sept, J 7.0 Hz), 2.87 (1H, sept, J 7.0 MHz), 1.30(6H, d, J 7.0 Hz) and 1.25 (6H, d, J 7.0 Hz), and6-isopropyl-2-pyridinemethanol (900 mg, 13%) as a colourless oil.

[0391] The following novel compound was also synthesised from2-pyridinemethanol by Method AR.

[0392] 6-N-Propyl-2-Pyridinemethanol

[0393] NMR δ_(H) (400 MHz, CDCl₃) 7.58 (1H, t, J 7.5 Hz), 7.03 (2H, t, J7.5 Hz), 4.72 (2H, s), 4.15 (1H, br s), 2.77 (2H, t, J 7.5 Hz), 1.77(2H, sept, J 7.5 Hz) and 0.97 (3H, t, J 7.5 Hz).

[0394] Method AS

[0395] Tert-Butyl5-Amino-7-(2-Furyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidine-3-Carboxylate(Example 203)

[0396] A solution of7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (300 mg, 1.49mmol) in DMF (5 mL), at 0° C., was treated with 60% sodium hydride inmineral oil (60 mg, 1.49 mmol), stirred for 30 minutes, treated withtert-butyl 4-(bromomethyl)phenylcarbonate (471 mg, 1.64 mmol), stirredat room temperature for 16 h, and purified by chromatography [SiO₂;EtOAc:heptane, (1:2)] to give the title compound (55 mg, 12%) as a beigesolid.

[0397] Method AT

[0398]2-(5-Amino-7-(2-Furyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidin-3-Yl)-1-Phenylethanone(Example 211)

[0399] A solution of7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (101 mg, 0.5mmol) in DMP (2 mL) was treated with 2-bromoacetophenone (100 mg, 0.5mmol) and triethylamine (105 μL, 0.75 mmol), stirred at room temperaturefor 3 days, diluted with water (100 mL) and filtered. The resultingsolid was purified by chromatography [SiO₂; Hexane: EtOAc, (3:1 to 1:1)]to give the title compound (20 mg, 13%) as a yellow solid.

[0400] Method AU

[0401]7.(2-Furyl)-3-(6-Hydroxymethyl2-Pyridylmethyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidine-5-AmineHydrochloride (Example 213)

[0402] A solution of6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)pyridine-2-carboxaldehyde(62 mg, 0.193 mmol) in MeOH (20 mL) was treated with acetic acid (5 mL),dimethylamine (2-M in MeOH, 1.93 mL, 3.86 mmol) and sodiumcyanoborohydride (242 mg, 3.86 mmol), stirred for 16 h and concentratedin vacuo. The residue was treated with saturated NaHCO₃ solution (20mL), extracted with EtOAc (3×10 mL) and the combined organic phase dried(MgSO₄), concentrated in vacuo and purified by chromatography [SiO₂;EtOAc] to give the free base as a yellow solid. The solid was suspendedin MeOH (1 mL), treated with HCl (4-M in dioxane, 0.25 mL), stirred for10 min, concentrated in vacuo and triturated with Et₂O to give the titlecompound (22 mg, 29%) as a yellow solid.

[0403] Method AV

[0404]3-(6-Cyanomethyl-2-Pyridylmethyl)-7-(2-Furyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidine-5-Amine(Example 220)

[0405] A solution of3-(6-bromomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(200 mg, 0.517 mmol) and sodium cyanide (51 mg, 1.03 mmol) in DMP (5 mL)was stirred at 60° C. for 16 h, poured into water (40 mL), extractedwith EtOAc (3×8 mL), the combined organic phase dried (MgSO₄),concentrated in vacuo and purified by chromatography[SiO₂;isohexane:EtOAc (1:1)] to give title compound (50 mg, 26%) as ayellow solid.

[0406] Method AW

[0407]3-(4-Hydroxybenzyl)-7-(2-Furyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidine-5-Amine(Example 221)

[0408] A solution of7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine—amine (400 mg, 1.98mmol) in DMP (3 mL), at 0° C., was treated with 60% sodium hydride inmineral oil (80 mg, 1.98 mmol), stirred for 30 min, treated with4-(2-(trimethylsilyl)ethoxymethoxy)benzyl bromide (1.23 g, 3.96 mmol),stirred at room temperature for 48 h and purified by chromatography[SiO₂; EtOAc:heptane, (1:2)]. The resulting yellow solid was dissolvedin MeOH:DMP (1:2), passed through an ion exchange cartridge (Isolute SPESCX-2), concentrated in vacuo, and washed with water and ether to givethe title compound (41 mg, 7%) as a pale yellow solid.

[0409] Method AX

[0410]N-(3(5-Amino-7-(2-Furyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidin-3-Ylmethyl)Phenyl)Propanesulphonamide(Example 224)

[0411] A solution of7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (153 mg, 0.5mmol) in pyridine (2 mL) at 0° C. was treated with propanesulfonylchloride (62 μL, 0.55 mmol) and shaken at room temperature for 16 h. Themixture was poured into water (50 mL), extracted with EtOAc (2×10 mL),washed with 10% citric acid (10 mL) and the combined organic phase dried(MgSO₄) and concentrated in vacuo to give the title compound (111 mg,54%) as a cream solid.

[0412] Method AY

[0413]7-(2-Furyl)-3-(6-(N-Methylanino)Methyl-2-Pyridylmethyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidine-5-Amine(Example 226)

[0414] A solution of N-methyl-2,2,2-trifluoroacetamide (197 mg, 1.55mmol) in DMP (5 mL) at 0° C. was treated with sodium hydride (60%dispersion in mineral oil; 62 mg, 1.55 mmol), stirred for 15 min,treated with3-(6-bromomethyl-2-pyridylmethyl)-7-(2-furyl)-3-H[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(120 mg, 0.310 mmol), stirred at 50° C. for 1 h, cooled to roomtemperature, poured into water (20 mL), extracted with EtOAc (3×10 mL)and the combined organic phase dried (MgSO₄) and concentrated in vacuoto giveN-(6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyimidin-3-ylmethyl)-2-pyridylmethyl)-N-methyltrifluoroacetamide.A solution of this product in MeOH (20 mL) was treated with a solutionof sodium (71 mg, 3.10 mmol) in MeOH (10 rL), stirred for 16 h,concentrated in vacuo, treated with EtOAc (20 mL), filtered throughCelite and concentrated in vacuo. The resulting solid was suspended inMeOH (2 mL), treated with HCl (4-M in dioxane, 1.0 mL), stirred for 10min, concentrated in vacuo and triturated with Et₂O to give the titlecompound (80 mg, 58%) as a yellow solid.

[0415] Method AZ

[0416]3-(1H-Benzotriazol-5-ylmethyl)-7-(2-Furyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidine-5-Amine(Example 158)

[0417] A mixture of 5-methyl-1H-benzotriazole (666 mg, 5 mmol) in THF(20 mli) was treated with NaH (60% dispersion, 200 mg, 5 mmol), stirredat room temperature for 10 min, treated with di-tert-butyl dicarbonate(115 mg, 5 mmol) and stirred overnight. The mixture was treated withsaturated NaHCO₃ solution (10 mL), extracted with EtOAc (2×10 mL), driedMgSO₄), filtered through a plug of SiO₂ and concentrated in vacuo togive tert-butyl 5-methylbenzotriazole-1-carboxylate (as a mixture withthe 6-methyl regioisomer) (1.08 g, 92%) as a colourless oil.

[0418] A solution of tet-butyl 5-methyl-1H-benzotriazole-l-carboxylate(as a mixture with the 6-methyl regioisomer) (1.08 g, 4.63 mmol),benzoyl peroxide (112 mg, 0.46 mmol) and N-bromosuccinnimide (0.76 g,4.63 mmol) in CC₁₄ (25 mL) was refluxed overnight, cooled, filtered,concentrated in vacuo and purified by chromatography [SiO₂;isohexane:EtOAc (10:1)] to give tert-butyl5-(bromomethyl)-1H-benzotriazole-l-carboxylate (666 mg, 46%) (as amixture with the 6-bromomethyl regioisomer) as a colourless oil.

[0419] A solution of7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine (404 mg, 2 mmol)in DMF (4 mL) was treated with NaH (60% dispersion, 80 mg, 2 mnmol),stirred at room temperature for 10 min, treated with a solution oftert-butyl 5-(bromomethyl)1H-benzotriazole-1-carboxylate (as a mixturewith the 6-bromomethyl regioisomer) (624 mg, 2 mmol) in DMF (2 mL) andstirred overnight. The mixture was concentrated in vacuo and purified bychromatography [SiO₂, isohexane:EtOAc (2:1)] to give tert-butyl5-(5-amino-7-(2-furyl)-3H-triazolo[4,5-d]pyrimidin-3-yl)methyl-1H-benzotriazol-1-carboxylate(135 mg, 24%) (as a mixture with the 6-substituted regioisomer) as awhite solid.

[0420] A solution of tert-butyl5-(5-amino-7-(2-furyl)-3H-triazolo[4,5-d]pyrimidin-3-yl)methyl-1H-benzotriazol-1-carboxylate(as a mixture withthe 6-substituted regioisomer) (135 mg, 0.31 mmol) inMeOH (5 mL) and TBF (5 mL) was treated with 40% aqueous dimethylamine(0.176 mL, 1.56 mmol), refluxed for 25 min, concentrated in vacuo andthe resulting solid triturated with ether, filtered, triturated withMeOH, filtered and dried to give the title compound (31 mg, 30%) as ayellow solid.

[0421] Method BA

[0422] Ethyl4-((5-Amino-7-(2-Furyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidine-3-Yl)Methyl)-2-Methylphenylcarbamate(Example 274)

[0423] A suspension of3-(4-amino-3-methylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(260 mg, 0.812 mmol) in pyridine (5 mL) at room temperature was treateddropwise with ethyl chloroformate (0.155 mL, 1.62 mmol), stirred for 30min, poured into water (30 mL), extracted with EtOAc (2×10 mL) and thecombined organic phase was dried (MgSO₄) and concentrated in vacuo togive the title compound (318 mg, 100%) as a beige solid.

[0424] Method BB

[0425]N-(4-(5-Amino-7-(2-Furyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidin-3-Ylmethyl)-2-Methylphenyl)Formamide(Example 244)

[0426] A mixture of ethyl4-((5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-yl)methyl(318 mg, 0.81 mmol) and LiMH₄ (62 mg, 1.62 mmol) in dry THF (30 mL) wasrefluxed overnight, cooled to room temperature, treated with 13% aqueousNaOH solution (0.1 mL) then water (0.3 mL), stirred for 30 min, filteredthrough Celite and concentrated in vacuo. The resulting solid wastriturated with THF and filtered to give the title compound (20 mg, 7%)as a yellow solid.

[0427] Method BC

[0428] 7-Fluoro-5-Methylindole

[0429] A solution of chloral hydrate (7.3 g, 44 mmol), sodium sulphatedecahydrate (52 g, 160 mmol) and H₂O (100 mL) was added slowly to astird solution of 2-fluoro4-methylamine (5.0 g, 40 mmol), hydroxylaminehydrochloride (11.1 g, 160 mmol) and conc. HCl (3 mL) in H₂O (50 mTL).The reaction mixture was refluxed for 1 h, stirred at room temperaturefor 5 h, filtered and the resulting solid crystallised from MeOH/H₂O toyield brown crystals (1.53 g). This material was added in small portionswith stirring to conc. sulphuric acid (20 mL) at 70° C., stirred for 1h, then added slowly with rapid stirring to ice/H₂O (200 mL), extractedtwice with EtOAc (2×25 mL) and the combined organic phase dried (MgSO₄)and concentrated in vacuo to give 7-fluoro-5-methylisatin (1.68 g, 24 %)as a dark red gum.

[0430] A solution of 7-fluoro-5-methylisatin (1.68 g, 9.43 mmol) in dryTlF (50 mL) was added slowly to an ice cold, stirred suspension ofLiAlH₄ (1.18 g, 31 mmol) in dry TBF (50 mL), refluxed for 2 h, cooled toroom temperature then treated sequentially with H₂O (1.2 mL), 15% NaOH(1.2 mL) and H₂O (3 mL). The solution was filtered through a pad ofCelite, washing the filter cake thoroughly with TFH, the deep bluefiltrate was concentrated in vacuo and purified by chromatography [SiO₂;iso-Hexane:EtOAc (9:1)] to give the title compound (480 mg, 41%) as apale blue oil; NMR 5H (CDCl₃) 8.19 (1H, br s), 7.21-7.16 (2H, m), 6.74(1H, d, J 12.0 Hz), 6.51-6.46 (1H, m) and 2.42 (3H, s).

[0431] Method BE

[0432]3-(7-Fluoro-5-Indolyl)-7-(2-Furyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidine-5-Amine(Example 246)

[0433] A stirred suspension of7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyriridine-5-amine (303 mg, 1.5mmol) in DMF (2 mL) was treated with NaH (60% dispersion in oil, 60 mg,1.5 mmol), stirred for 10 min, treated slowly with a solution oftert-butyl 5-bromomethyl-7-fluoroindole-1-carboxylate (460 mg, 1.5 mmol)in DMF (1 mL), stirred for 2 h then the mixture was purified directly bychromatography [SiO₂; iso-hexarie:EtOAc (2:1)] to give the BOC protectedproduct (180 mg, 0.417 mmol) as a pale green solid. This material wasdissolved in MeOH (5 mL), treated with sodium methoxide (113 mg, 2mmol), refluxed for 4 h, cooled to room temperature, diluted with H₂Oand filtered to give the title compound (118 mg, 81%) as a cream solid.

[0434] Method BF

[0435]3-(3(4-Fluorobenzylanno)Benzyl)-7-(2-Furyl)-3H-[1,2,3]Triazolo[4,5-D]Pyrimidine-5-Amine(Example 252)

[0436] A suspension of3-(3-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(200 mg, 0.65 mmol) and 4A molecular sieves in ThF (10 mL) was treatedwith 4-fluorobenzaldehyde (0.04 mL, 0.37 mmol), heated to 40° C. for 3h, cooled to room temperature, treated sodium triacetoxyborohydride (400mg, 1.89 mmol) and acetic acid (0.1 mL) and stirred for 15 minutes. Thereaction was quenched by addition of sat. NaHCO₃ (5 mL), extracted withEtOAc (2×5 mL) and the combined organic phase dried (MgSO₄),concentrated in vacuo and purified by chromatography [(SiO₂;EtOAc:Heptane (1:2)] to give the title compound (60 mg, 44%) as a whitesolid.

[0437] Method BG

[0438] 2-(2-Methoxyethyl)-6-(Triphenylmethoxy)Methylpyridine

[0439] A stirred solution of (methoxymethyl)triphenylphosphoniumchloride (2.79 g, 8.13 mmol) in THP (50 mL) at 0° C. was treateddropwise with n-BuLi (1.6-M in hexanes, 5.08 mL, 8.13 mmol), stiered for1 h, treated with a solution of6-(triphenylmethoxy)methylpyridine-2-carboxaldehyde (1.54 g, 4.06 mmol)in THF (15 mL) and allowed to warm to room temperature overnight. Thereaction was treated with saturated NH₄Cl solution (5 mL), diluted withwater (50 mL), extracted with EtOAc (2×50 mL) and the combined organicphase diluted with iso-hexane (50 mL), dried (MgSO₄), filtered throughsilica and concentrated in vacuo to give2-(2-methoxyethenyl)-6-(triphenylmethoxy)methylpyridine (1.58 g) as ayellow oil. A solution of this crude alkene and 10% Pd/C (216 mg, 0.203mmol) in EtOAc (50 mL) was stirred under a hydrogen atmosphere for 16 h,filtered through Celite and concentrated in vacuo to give the titlecompound (1.08 g, 65%) as a yellow oil; NMR SH (400 M , CDCl₃) 7.67-7.64(1H, m), 7.52-7.49 (6H, m), 7.32-7.21 (10H, m), 7.09-7.07 (1H, m), 4.34(2H, s), 3.69 (2H, t, J 6.5 Hz), 3.32 (3H, s) and 2.98 (2H, t, J 6.5Hz); M/Z 410 (M+H)⁺.

[0440] Method BH

[0441] 2-Bromomethyl-6-(2-Methoxyethyl)Pyridine

[0442] A solution of2-(2-methoxyethyl)-6-(triphenylmethoxy)methylpyridine (1.08 g, 2.64mmol) in 4-M HCl in dioxan (10 mL, 40.0 mmol) was stirred for .4 h andconcentrated in vacuo. The residue was partitioned betweendichloromethane (15 mL) and saturated NaHCO₃ solution (15 mL), theaqueous phase was extracted with dichloromethane (10 mL) and thecombined organic phase was dried (MgSO₄) and concentrated in vacuo togive 6-(2-methoxyethyl)pyridine-2-methanol. A solution of this productin dichloromethane (40 mL) at 0° C. was treated with triphenylphosphine(830 mg, 3.16 mmol) followed portion wise by carbon tetrabromide (1.31g, 3.96 rnmol), stirred for 1 h, concentrated in vacuo and purified bychromatography [SiO₂; isohexane:EtOAc (4:1)] to give the title compound(303 m g, 50%) as a yellow oil; NMR δ_(H) (400 MHZ, CDCl₃) 7.60 (1H, t,J 7.5 Hz), 7.28 (1H, d, J 7.5 Hz), 7.13 (1H, d, J 7.5 Hz), 4.53 (2H, s),3.76 (2H, t, J 6.5 Hz), 3.35 (3H, s) and 3.05 (2H, t, J 6.5 Hz).

[0443] Experimental Data for Examples 1-274 are Provided in Table 2.

[0444] HPLC is carried out using the following conditions: Column.Waters Xterra RP 18 (50×4.6 mm); Particle size 5 μM; Mobile phase MeOH:10 mM aq NH₄OAc (pH 7 buffer); Gradient 50:50 isocratic for 1 min. thenlinear gradient 50:50 to 80:20 over 5 min. then 80:20 isocratic for 3min.; Flow rate 2.0 mL/min.; Detection wavelength λ=230 nM. Retentiontimes are provided in Table 2. TABLE 2 Example Method Yield(%) PhysicalData 1 A 65 IR ν_(max)(Nujol)/cm⁻¹ 3403, 3329, 3134, 2925, 1656, 1634,1582, 1565, 1463 and 1377; NMR δ_(H)(400MHz, DMSO) 6.83-6.87(1H, m),7.12(2H, s), 7.89(1H, d, J 3.1Hz), 8.09-8.10(1H, m), 15.52(1H, s); M/Z203(M+H)⁺. 2 B 11 IR ν_(max)(Nujol)/cm⁻¹ 2924, 2854, 1612, 1587, 1526,1489, 1456, 1372, 1221 and 753; NMR δ_(H)(400MHz, DMSO) 4.98(2H, s),5.14(2H, s), 5.71(2H, s), 6.85-6.87 (1H, m), 7.00-7.14(3H, m),7.14-7.46(9H, m), 7.89(1H, d, J 3.5Hz), 8.16(1H, d<J 1.0Hz); Anal. Calcdfor C₂₉H₂₁F₃N₆O. 0.25 H₂O: C, 65.59; H, 4.08; N, 15.83. Found: C, 65.46;H, 4.03; N, 15.76. 3 B 22 IR ν_(max)(Nujol)/cm⁻¹ 3480, 3312, 3195, 3118,2925, 2854, 1652, 1609, 1581, 1487, 1456, 1436, 1027 and 759; NMRδ_(H)(400MHz, DMSO) 5.60(2H, s), 6.84-6.86 (1H, m), 7.15-7.29(3H, m),7.32-7.43(3H, m), 7.89(1H, d, J 2.9Hz), 8.12(1H, s). 4 B 9 mp221.0-221.1° C.; IR ν_(max)(Nujol)/cm⁻¹ 3470, 3310, 3191, 3144, 2924,2854, 1642, 1610, 1521, 1463 and 1354; NMR δ_(H)(400MHz, DMSO) 5.85(2H,s), 6.87(1H, s), 7.37(2H, s), 7.63-7.73(2H, m), 7.91(1H, d, J 2.8Hz),8.13(1H, s), 8.18(1H, s), 8.20(1H, s). Anal. Calcd for C₁₅H₁₁N₇O₃: C,50.57; H, 3.11; N, 27.52. Found: C, 50.99; H, 3.23; N, 27.21. 5 C 92 mp259.8-259.9° C.; IR ν_(max)(Nujol)/cm⁻¹ 3452, 3367, 3318, 3185, 3142,2922, 1651, 1602, 1514, 1463 and 1377; NMR δ_(H)(400MHz, DMSO) 5.09(2H,s), 5.49(2H, s), 6.35(1H, s), 6.41(1H, d, J 7.5Hz), 6.45(1H, d, J8.0Hz), 6.85-6.86 (1H, m), 6.96(1H, t, J 8.0Hz), 7.30(2H, s), 7.90(1H,d, J 3.5Hz), 8.11 (1H, s). Anal. Calcd for C₁₅H₁₃N₇O: C, 56.63; H, 4.50;N, 30.82. Found: C, 56.82; H, 4.25; N, 30.57. 6 B 21 IRν_(max)(Nujol)/cm⁻¹ 3405, 3328, 3211, 3155, 2925, 2854, 1719, 1603,1577, 1463, 1023 and 731; NMR δ_(H)(400MHz, DMSO) 3.84(3H, s), 5.76(2H,s), 6.85-6.87 (1H, m), 7.33-7.38(2H, s), 7.50-7.59(2H, m), 7.89-7.92(3H,s), 8.12-8.13 (1H, m); Anal. Calcd for C₁₇H₁₄N₆O₃.0.25 H₂O: C, 57.54; H,4.12; N, 23.68. Found: C, 57.42; H, 3.75; N, 23.37. 7 B 27 IRν_(max)(Nujol)/cm⁻¹ 3506, 3309, 3189, 3131, 2925, 2854, 1635, 1606,1580, 1502, 1417, 1204, 1025 and 762; NMR δ_(H)(400MHz, DMSO) 3.70(6H,s), 5.58 (2H, s), 6.44(3H, s), 6.84-6.87(1H, m), 7.34(2H, s), 7.90(1H,d, J 3.5Hz), 8.11-8.12(1H, m); Anal. Calcd for C₁₇H₂₁₆N₆O₃.0.5 H₂O: C,56.50; H, 4.74; N, 23.26. Found: C, 56.44; H, 4.56; N, 22.98. 8 B 21 IRν_(max)(Nujol)/cm⁻¹ 3488, 3314, 3146, 2922, 2853, 1667, 1608, 1583, 1463and 1378; NMR δ_(H)(400MHz, DMSO) 5.79(2H, s), 6.84-6.87(1H, m),7.01(1H, d, J 4.0Hz), 7.05(1H, d, J 4.0Hz), 7.38(2H, s), 7.89(1H, d, J3.5Hz), 8.11-8.13 (1H, m). 9 D 14 IR ν_(max)(Nujol)/cm⁻¹ 3458, 3299,3174, 3111, 2923, 1625, 1605, 1463 and 1377; NMR δ_(H)(400MHz, DMSO)3.61(3H, s), 5.58(2H, s), 6.84-6.94(3H, m), 7.06-7.11 (1H, d, J 8.5Hz),7.19(1H, t, J 8.0Hz), 7.34(2H, s), 7.64-7.67(2H, m), 7.91(1H, d, J3.0Hz), 8.12(1H, s), 10.21(1H, s); Anal. Calcd for C₂₉H₂₁F₃N₆O.0.25 H₂O:C, 65.59; H, 4.08; N, 15.83. Found: C, 65.46; H, 4.03; N, 15.76. 10 E 18IR ν_(max)(Nujol)/cm⁻¹ 3404, 3313, 3202, 3122, 2923, 2854, 1724, 1639,1609, 1557, 1456, 1407 and 1379; NMR δ_(H)(400MHz, DMSO) 4.60(2H, d, J6.0Hz), 6.86-6.89(1H, m), 7.25-7.32(1H, m), 7.33-7.44(4H, m), 7.67(2H,s), 7.91 (1H, d, J 3.5Hz), 8.14-8.16(1H, m), 9.25(1H, t, J 6.0Hz). 11 B40 IR ν_(max)(Nujol)/cm⁻¹ 3327, 3207, 2924, 2854, 1650, 1602, 1583,1566, 1513 and 1487; NMR δ_(H)(400MHz, DMSO) 3.72(3H, s), 5.63(2H, s),6.80(1H, d, J 7.5Hz), 6.85-6.89(3H, m), 7.26(1H, t, J 7.5Hz), 7.33(2H,s), 7.90(1H, d, J 3.5Hz), 8.11(1H, s); Anal. Calcd for C₁₆H₁₄N₆O₂.0.25H₂O: C, 58.80; H, 4.47; N, 25.71. Found: C, 58.90; H, 4.40; N, 25.75. 12B 21 IR ν_(max)(Nujol)/cm⁻¹ 3374, 3311, 3202, 1636, 1606, 1586, 1530,1511, 1465, 1439, 1377 and 1343: NMR δ_(H)(400MHz, DMSO) 6.03(2H, s),6.86-6.89(1H, m), 6.98(1H, d, J 7.5Hz), 7.36(2H, s), 7.60-7.73(2H, m),7.92(1H, d, J 3.5Hz), 8.14(1H, s), 8.2(1H, d, J 8.0Hz); Anal. Calcd forC₁₅H₁₁N₇O₃.0.35 H₂O: C, 52.43; H, 3.43; N, 28.54. Found: C, 52.51; H,3.33; N, 28.21. 13 C 67 IR ν_(max)(Nujol)/cm⁻¹ 3489, 3313, 3191, 1638,1603, 1505, 1460 and 1378; NMR δ_(H)(400MHz, DMSO) 5.27(2H, s), 5.47(2H,s), 6.50(1H, t, J 7.5Hz), 6.67-6.78 (2H, m), 6.86(1H, s), 7.01(1H, t, J7.0Hz), 7.36(2H, s), 7.90(1H, d, J 3.0Hz), 8.12(1H, s). 14 F 35 IRν_(max)(Nujol)/cm⁻¹ 3447, 3327, 3205, 2922, 2853, 1725, 1652, 1611 and1458; NMR δ_(H)(400MHz, DMSO) 8.13(1H, d, J 1.0Hz), 7.90(1H, d, J3.5Hz), 7.38 (2H, s), 6.87-6.85(1H, m), 5.40(2H, s), 4.18(2H, q, J7.0Hz) and 1.21(3H, t, J 7.0Hz); Anal. Calcd for C₁₂H₁₂N₆O₂+0.2 H₂O: C,49.38; H, 4.28, N, 28.79. Found: C, 49.25; H, 4.09; N, 28.47. 15 B 15 IRν_(max)(Nujol)/cm⁻¹ 3490, 3307, 3189, 2230, 1959, 1728, 1642, 1611,1583, 1565, 1463, 1377, 1283, 1234, 1030 and 761; NMR δ_(H)(400MHz,DMSO) 5.75 (2H, s), 6.82-6.89(1H, m), 7.35(2H, s), 7.57-7.59(2H, m),7.79-7.81(2H, m), 7.91(1H, d, J 3.5Hz), 8.12(1H, s). 16 B 6 IRν_(max)(Nujol)/cm⁻¹ 3309, 3184, 2726, 1639, 1608, 1585, 1456, 1377,1026, 1002, 953 and 750; NMR δ_(H)(4.00MHz, DMSO) 2.22(2H, quin, J7.0Hz), 2.67 (2H, t, J 7.0Hz), 4.45(2H, t, J 7.0Hz), 6.83-6.88(1H, m),7.23-7.35(3H, m), 7.66(1H, dt, J 8.0, 2.0Hz), 7.89(1H, dd, J 3.5,1.0Hz), 8.10-8.13(1H, m); Anal. calcd for C₁₆H₁₅N₇O.0.6 H₂O: C, 57.86;H, 4.92; N, 29.52. Found: C, 57.58; H, 4.53; N, 29.66. 17 B 7 IRν_(max)(Nujol)/cm⁻¹ 3379, 3336, 3208, 1655, 1604, 1513, 1456, 1325,11687, 1124, 1025 and 755; NMR δ_(H)(400MHz, DMSO) 5.79(2H, s),6.83-6.88(1H, m), 7.36(2H, s), 7.53(1H, d, J 7.5Hz), 7.60(1H, t, J7.5Hz), 7.67-7.76(2H, m), 7.91(1H, d, J 3.5Hz), 8.13(1H, s); Anal.Calcd. for C₁₆H₁₁F₃N₆O: C, 53.34; H, 3.08; N, 23.31. Found: C, 53.38; H,3.18; N, 23.15. 18 G 100 IR ν_(max)(Nujol)/cm⁻¹ 3451, 3206, 2361, 2261,1655, 1604, 1459, 1378, 1195, 1028 and 774; NMR δ_(H)(400MHz, DMSO)5.57(2H, s), 6.57-6.63(1H, m), 6.65-6.74(2H, m), 6.83-6.88(1H, m),7.14(1H, t, J 7.5Hz), 7.91(1H, d, J 3.0Hz), 8.12(1H, d, J 1.0Hz). 19 J77 mp 291.8-292.0° C.; IR ν_(max)(DR)/cm⁻¹ 3436, 3178, 1651, 1615, 1398,1226, 1029 and 977; NMR δ_(H)(400MHz, DMSO) 15.5-15.3(1H, br s),7.84(1H, d, J 3.5Hz), 7.07(2H, br s), 6.48(1H, dd, J 3.5, J 1.0Hz),2.44(3H, s). 20 B 47 mp 213.5.-213.7° C.; IR ν_(max)(DR)/cm⁻¹ 3300,3218, 3098, 2957, 2927, 2744, 2368, 1645, 1602, 1570, 1537, 1508, 1490,1438, 1328 and 1233; NMR δ_(H)(400MHz, DMSO) 7.86(1H, d, J 3.0Hz),7.43-736(1H, m), 7.31(2H, br s), 7.28-7.15 (3H, m), 6.50(1H, dd, J 1.0,J 3.5Hz), 5.68(2H, s) and 2.45(3H, s). 21 K 99 IR ν_(max)(DR)/cm⁻¹ 3151,2360, 1654, 1182, 998, 824, 681, and 572; NMR δ_(H) (400MHz, DMSO)10.28(1H, d, J 2.0Hz) and 9.73(1H, d, J 2.5Hz) 22 A 8 IRν_(max)(DR)/cm⁻¹ 3479, 3289, 3169, 1597, 1502, 1226, 1119, 999, 880 and757; NMR δ_(H)(400MHz, DMSO) 9.43(1H, s), 9.25(1H, s), 7.48-7.34(3H, m)7.30-7.22 (2H, m), 7.21-7.15(1H, m) and 5.72(2H, s). 23 B 20 mp187.3-187.7° C.; IR ν_(max)(DR)/cm⁻¹ 3993, 3489, 3319, 3197, 2951, 2725,2353, 1954, 1719, 1633, 1604, 1503, 1420, 1232, 1032 and 740; NMRδ_(H)(400MHz, DMSO) 2.27(3H, s) 5.62(2H, s), 6.82-6.88(1H, m),7.02-7.16(3H, m), 7.24(1H, t, J 7.5Hz), 7.33(2H, s), 7.90(1H, d, J3.5Hz) 8.12(1H, s). 24 N 46 mp 196.9-197.1° C.; IR ν_(max)(DR)/cm⁻¹3448, 3321, 3200, 1649, 1616, 1509, 1488; NMR δ_(H)(400MHz, DMSO)8.49-8.47(1H, m), 8.12-8.11(1H, m), 7.91 (1H, d, J 3.5Hz), 7.81-7.77(1H,m), 7.34-7.30(1H, m), 7.27(2H, br s), 7.24 (1H, d, J 8.0Hz),6.86-6.85(1H, m), 5.77(2H, s). 25 N 50 IR ν_(max)(DR)/cm⁻¹ 3326, 3211,2956, 2856, 1641, 1612, 1507, 1491; NMR δ_(H) (400MHz, CDCl₃)8.77-8.76(1H, m), 8.58-8.56(1H, m), 8.08(1H, d, J 3.5Hz), 7.78(1H, m),7.75-7.72(1H, m), 7.29-7.25(1H, m), 6.71-6.69(1H, m), 5.68(2H, s),5.37(2H, br s); Anal. Calcd for C₁₄H₁₁N₇O.0.2 H₂O.0.4 C₄H₃O₂: C, 56.41;H, 4.43, N, 29.52. Found: C, 56.10; H, 4.33; N, 29.52. 26 O 85 mp291.0-291.1° C.; IR ν_(max)(Nujol)/cm⁻¹ 3401, 3317, 3205, 2995, 1714,1646, 1615, 1587, 1483 and 1247; NMR δ_(H)(400MHz, DMSO) 13.58-13.31(1H,s), 8.12(1H, s), 7.91(1H, d, J 3.5Hz), 7.36(2H, s), 6.87-6.86(1H, m) and5.29 (2H, s); Anal. Calcd for C₁₀H₈N₆O₃.0.6 H₂O: C, 44.32; H, 3.42, N,31.01. Found: C, 44.26; H, 3.07; N, 30.74. 27 B 19 mp 209.9-210.1° C.;IR ν_(max)(DR)/cm⁻¹ 3504, 3312, 3201, 2948, 1611, 1503, 1435, 1279,1220, 1025 and 755; NMR δ_(H)(400MHz, DMSO) 5.69(2H, s), 6.82-6.87 (1H,m), 7.19-7.25(1H, m), 7.33(2H, s), 7.37-7.40(3H, m), 7.90(1H, d, J3.5Hz), 8.10-8.13(1H, m). Anal. Calcd for C₁₅H₁₁N₆OCl.0.2 H₂O: C, 54.54;H, 3.48; N, 25.44. Found: C, 54.69; H, 3.33; N, 25.09. 28 K 40 IRν_(max)(DR)/cm⁻¹ 3282, 2852, 1630, 1368, 1120, 871 and 618; NMRδ_(H)(400MHz, DMSO) 7.94(1H, d, J 2.5Hz), 7.45-7.36(2H, m),7.29-7.22(2H, m), 7.21-7.16(1H, m) and 5.71(2H, s). 29 B 8 IRν_(max)(DR)/cm⁻¹ 3999, 3483, 3438, 3310, 3207, 2950, 2732, 2452, 1846,1657, 1486, 1312, 1030 and 754; NMR δ_(H)(400MHz, DMSO) 4.02(3H, s),6.81-6.88 (1H, m), 7.25(2H, s), 7.88(1H, d, J 3.5Hz), 8.09-8.11(1H, m).30 P 39 IR ν_(max)(Nujol)/cm⁻¹ 3500-3200, 2946, 2835, 1700 and 1523; NMRδ_(H)(400MHz, DMSO) 8.11(1H, s), 7.89(1H, d, J 3.5Hz), 7.69(1H, s),7.34(1H, s), 7.26(2H, s), 6.87-6.84(1H, m) and 5.08(2H, s). 31 P 48 IRν_(max)(Nujol)/cm⁻¹ 3457, 3313, 1666, 1617, 1523 and 1442; NMRδ_(H)(400MHz, DMSO) 10.68(1H, s), 8.12(1H, s), 7.91(1H, d, J 3.5Hz),7.75(1H, s), 7.45(1H, d, J 8.0Hz), 7.37(1H, t, J 8.0Hz), 7.30(2H, s),7.15(1H, d, J 8.0Hz), 6.88-6.84(1H, m and 5.39(2H, s); Anal. Calcd forC₁₆H₁₂N₇O₂Cl.0.8 H₂O: C, 50.02; H, 3.57, N, 25.27. Found: C, 50.15; H,3.48; N, 25.12. 32 N 76 mp 191.4-192.0° C.; IR ν_(max)(DR)/cm⁻¹ 3511,3306, 3194, 2955, 1638, 1476; NMR δ_(H)(400MHz, DMSO) 8.12-8.11(1H, m),7.91(1H, dd, J 3.5, 1.0Hz), 7.66(1H, dd, J 8.0, 7.0Hz), 7.27(2H, br s),6.87-6.85(1H, m), 6.73-6.70(2H, m), 5.69(2H, s), 3.68(3H, s); Anal.Calcd for C₁₅H₁₃N₇O₂.0.2 C₄H₈O₂: C, 55.66; H, 4.32, N, 28.76. Found: C,55.88; H, 4.17; N, 28.59. 33 B 11 mp 204.1-204.2° C.; IRν_(max)(DR)/cm⁻¹ 3490, 3321, 3200, 2923, 2711, 2490, 1749, 1605, 1502,1376, 1272, 1034 and 761; NMR δ_(H)(400MHz, DMSO) 5.83 (2H, s),6.83-6.86(1H, m), 7.01(1H, dd, J 5.0, 3.5Hz), 7.16(1H, dd, J 3.5,1.0Hz), 7.34(2H, s), 7.48(1H, dd, J 5.0, 1.5Hz), 7.89(1H, d, J 3.5Hz),8.09-8.12 (1H, m). 34 Q 30 mp 225-230° C.; IR ν_(max)(DR)/cm⁻¹ 3520,3344, 1734, 1611, 1438, 1240, 996, 833 and 761; NMR δ_(H)(400MHz, DMSO)8.26(1H, d, J 3.0Hz), 8.15(1H, d, J 3.0Hz), 7.50-7.44(2H, br s),7.42-7.36(1H, m), 7.29-7.21(1H, m), 7.21-7.15 (1H, m) and 5.73(2H, s).35 H 51 mp 174.0-174.2° C.; IR ν_(max)(DR)/cm⁻¹ 3473, 3317, 3188, 2740,1736, 1648, 1243, 1004 and 752; NMR δ_(H)(400MHz, DMSO) 8.68(1H, dd, J4.0, 1.5Hz), 7.99(1H, dd, J 5.0, 1.0Hz), 7.43-7.35(2H, m), 7.31-7.16(5H,m) and 5.71 (2H, s). 36 C 50 mp 231.7-234.0° C.; IR ν_(max)(DR)/cm⁻¹3498, 3404, 3309, 2931, 1607, 1539, 1498, 1317, 1101 and 1027; NMRδ_(H)(400MHz, DMSO) 7.86(1H, dd, J 0.5, 3.5Hz), 7.24(2H, br s), 6.96(1H,t, J 7.8Hz), 6.50(1H, dd, J 1.0, 3.5Hz), 6.48-6.43 (1H, m),6.43-6.38(1H, m), 6.36(1H, t, J 1.7Hz), 5.46(2H, s), 5.07(2H, br s) and2.43(3H, s). 37 N 60 mp 200.8-218.9° C.; NMR δ_(H)(400MHz, DMSO)8.12-8.11(1H, m), 7.91 (1H, d, J 3.5Hz), 7.64(1H, t, J 7.5Hz), 7.29(2H,br s), 7.18(1H, d, J 7.5Hz), 6.90(1H, d, J 7.5Hz), 6.86-6.85(1H, m),5.70(2H, s) and 2.42(3H, s). 38 Q 35 mp 242.0-242.1° C.; IRν_(max)(DR)/cm⁻¹ 3513, 3294, 1570, 1234, 999 and 755; NMR δ_(H)(400MHz,DMSO) 7.96(1H, s), 7.46-7.34(3H, m), 7.30-7.13(3H, m), 5.72(2H, s) and2.60(3H, s). 39 B 26 IR ν_(max)(Nujol)/cm⁻¹ 3464, 3340, 3189, 2966,2748, 1692, 1643 and 1605; NMR δ_(H)(400MHz, DMSO) 8.11-8.09(1H, m),7.90(1H, d, J 3.5Hz), 7.33-7.24 (4H, m), 7.19-7.12(2H, m), 7.09(1H, s),6.86-6.84(1H, m), 5.64(2H, s), 4.07(2H, d, J 6.0Hz) and 1.33(9H, s). 40B 12 IR ν_(max)(Nujol)/cm⁻¹ 3474, 3323, 3184, 3006, 2971, 2941, 2837,1648, 1606 and 1496; NMR δ_(H)(400MHz, DMSO) 8.13-8.10(1H, m), 7.90(1H,d, J 3.5Hz), 7.32(2H, s), 6.98(1H, d, J 9.0Hz), 6.89-6.84(2H, m),6.48(1H, d, J 3.0Hz), 5.57(2H, s), 3.76(3H, s) and 3.62(3H, s). 41 B 32mp 213.8-213.9° C.; IR ν_(max)(DR)/cm⁻¹ 3996, 3654, 3507, 3320, 2930,2562, 2621, 1944, 1837, 1676, 1428, 1230, 1095, 1026 and 797; NMRδ_(H)(400MHz, DMSO) 5.65(2H, s), 6.81-6.86(1H, m), 7.16(2H, t, J 8.5Hz),7.31(2H, s), 7.44-7.56(1H, m), 7.86(1H, dd, J 3.5, 1.0Hz), 8.07-8.13(1H,m). Anal. Calcd for C₁₅H₁₀N₆OF₂: C, 54.88; H, 3.07; N, 25.59. Found: C,54.57; H, 3.05; N, 25.23. 42 Q 29 mp 265.7-26.2° C.; IR ν_(max)(DR)/cm⁻¹3491, 3370, 3120, 1614, 1232, 972, 753 and 514; NMR δ_(H)(400MHz, DMSO)7.72(1H, s), 7.51-7.43(2H, s), 7.42-7.35 (1H, m), 7.30-7.14(3H, m),5.73(2H, s) and 2.55(3H, s). 43 H 65 mp 281.1-280.2° C.; IRν_(max)(DR)/cm⁻¹ 3466, 3326, 1641, 1503, 1379, 1240, 1056, and 825; NMRδ_(H)(400MHz, DMSO) 15.5(1H, br s), 8.6(1H, dd, J 1.0, 4.0Hz), 7.96(1H,dd, J 1.0, 5.0Hz), 7.36(1H, dd, J 4.0, 5.0Hz) and 7.0(2H, br s). 44 S/T28 IR ν_(max)(DR)/cm⁻¹ 3255, 1686, 1590, 1458; NMR δ_(H)(400MHz, DMSO)11.24 (1H, s), 8.95-8.94(1H, m), 8.37-8.35(1H, m), 8.08-8.07(1H, m),7.96-7.95 (1H, m), 7.68(1H, d, J 8.0Hz), 6.85-6.84(1H, m). 45 A 59 mp190.4-190.8° C.; IR ν_(max)(DR)/cm⁻¹ 3322, 3162, 1665, 1576, 1351, 1119,1000, 809 and 604; NMR δ_(H)(400MHz, DMSO) 9.44(1H, s), 9.26(1H, s),8.24-8.16 (2H, m), 7.95(1H, s), 7.74-7.63(2H, m), 7.45(2H, br s) and5.87(2H, s). 46 K 99 IR ν_(max)(Nujol)/cm⁻¹ 2967, 1651 and 1463; NMRδ_(H)(400MHz, DMSO) 8.35-8.24 (3H, s), 8.14-8.11(1H, m), 7.91(1H, d, J3.5Hz), 7.47-7.39(2H, m), 7.36-7.31(2H, s), 6.88-6.84(1H, m), 5.67(2H,s) and 3.98(2H, q, J 5.5Hz); Anal. Calcd for C₁₆H₁₅N₇O.2HCl.0.9 H₂O: C,46.82; H, 4.62, N, 23.89. Found: C, 47.10; H, 4.40; N, 23.84. 47 B 26 IRν_(max)(Nujol)/cm⁻¹ 3375, 3194, 2929, 2753, 1732, 1657, 1515, 1400 and1334; NMR δ_(H)(400MHz, DMSO) 8.14-8.11(1H, m), 7.90(1H, d, J 3.0Hz),7.45-7.29 (6H, m), 6.88-6.84(1H, m), 5.71(2H, s), 2.95(3H, s) and2.85(3H, s); Anal. Calcd for C₁₈H₁₇N₇O₂.0.5 H₂O: C, 58.06; H, 4.87, N,26.33. Found: C, 58.16; H, 4.65; N, 26.06. 48 C 49 mp 265.9-266.0° C.;IR ν_(max)(DR)/cm⁻¹ 3448, 3363, 3316, 3189, 1645, 1597, 1511, 1440 and1103; NMR δ_(H)(400MHz, DMSO) 8.69(1H, dd, J 1.2, 3.7Hz), 7.95(1H, dd, J1.2, 5.0Hz), 7.38(1H, dd, J 3.9, 5.0Hz), 7.26(2H, br s), 6.97 (1H, t, J7.7Hz), 6.48-6.45(1H, m), 6.44-6.40(1H, m), 6.36(1H, t, J 1.7Hz),5.5(2H, s) and 5.11(2H, br s). 49 B 8 IR ν_(max)(Nujol)/cm⁻¹ 3488, 3319,2952, 1641, 1503 and 1420; NMR δ_(H)(400MHz, DMSO) 8.49-8.42(1H, m),8.14(1H, d, J 1.0Hz), 7.91(1H, d, J 3.5Hz), 7.78-7.71(2H, m),7.48-7.32(4H, m), 6.88-6.85(1H, m), 5.72(2H, s) and 2.75(3H, d, J4.5Hz). 50 C 60 mp 228.2-228.3° C.; IR ν_(max)(DR)/cm⁻¹ 3441, 3318,3197, 1738, 1648, 1515, 1122, 1006, 888 and 747; NMR δ_(H)(400MHz, DMSO)9.45(1H, s), 9.27(1H, s), 7.44(2H, br s), 6.97(1H, t, J 8.0Hz),6.49-6.39(2H, m), 6.35(1H, s), 5.52 (2H, s), and 5.13(2H, s). 51 N 70 mp182.9-183.1° C.; IR ν_(max)(DR)/cm⁻¹ 3488, 3311, 3199, 2943, 1611, 1504;NMR δ_(H)(400MHz, DMSO) 8.10(1H, d, J 3.5Hz), 7.78(1H, m), 7.01(1H, t, J9.0Hz), 6.79(1H, dt, J 9.0, 3.5Hz), 6.75-6.73(1H, m), 6.71-6.70(1H, m),5.70(2H, s), 5.38(2H, br s), 3.71(3H, s); Anal. Calcd forC₁₆H₁₃N₆O₂F.0.1 H₂O: C, 56.17; H, 3.89, N, 24.56. Found: C, 56.27; H,3.85; N, 24.22. 52 P 70 mp 263.8-264.0° C.; IR ν_(max)(Nujol)/cm⁻¹ 3305,3192, 1705, 1635 and 1442; NMR δ_(H)(400MHz, DMSO) 11.04(1H, s),8.37(1H, d, J 4.0Hz), 8.15-8.11 (1H, m), 7.96(1H, d, J 7.0Hz), 7.91(1H,d, J 3.0Hz), 7.79(1H, dt, J 7.5, 2.0Hz), 7.32(2H, s), 7.18-7.11(1H, m),6.88-6.85(1H, m) and 5.46(2H, s). 53 P 77 mp 256.1-256.4° C.; IRν_(max)(Nujol)/cm⁻¹ 3454, 3311, 2993, 1664, 1488 and 1439; NMRδ_(H)(400MHz, DMSO) 8.86(1H, t, J 6.0Hz), 8.50(1H, d, J 4.5Hz), 8.12(1H,s), 7.90(1H, d, J 3.5Hz), 7.79(1H, dt, J 7.5, 1.5Hz), 7.41-7.25(4H, m),6.88-6.84(1H, m) and 5.23(2H, s), 4.41(2H, d, J 6.0Hz); Anal. Calcd forC₁₆H₁₄N₈O₂.0.25 H₂O: C, 54.16; H, 4.12, N, 31.58. Found: C, 54.01; H,4.03; N, 31.44. 54 P 61 mp 292.2-292.3° C.; IR ν_(max)(Nujol)/cm⁻¹ 3433,3323, 2975, 2941, 1673 and 1446; NMR δ_(H)(400MHz, DMSO) 10.50(1H, s),8.13(1H, s), 7.92(1H, d, J 3.0Hz), 7.57(2H, d, J 7.5Hz), 7.37-7.27(4H,m), 7.08(1H, t, J 7.5Hz), 6.89-6.84 (1H, m) and 5.38(2H, s). 55 B 18 mp264.5-264.8° C.; IR ν_(max)(DR)/cm⁻¹ 4007, 3489, 3308, 3190, 1649, 1552,1433, 1349, 1227, 1082, 1030 and 729; NMR δ_(H)(400MHz, DMSO) 5.99(2H,s), 6.84-6.89(1H, m), 7.39(2H, s), 7.91(1H, d, J 3.5Hz), 8.11-8.15(1H,m), 8.59(2H, d, J 2.0Hz), 8.78(1H, t, J 2.0Hz). 56 B 30 IRν_(max)(DR)/cm⁻¹ 3508, 3300, 3181, 1611, 1572, 1504, 1420, 1352, 1225and 1030; NMR δ_(H)(400MHz, DMSO) 8.22-8.16(2H, m), 7.86(1H, d, J3.2Hz), 7.63-7.72(2H, m), 7.35(2H, br s), 6.50(1H, dd, J 1.0, 3.5Hz),5.82(2H, s) and 2.45(3H, s). 57 B mp 188.8-188.9° C.; IRν_(max)(Nujol)/cm⁻¹ 3492, 3302, 3189, 2951, 1635 and 1505; NMRδ_(H)(400MHz, DMSO) 8.14-8.10(1H, m), 7.90(1H, d, J 3.0Hz),7.47-7.32(3H, m), 7.20(1H, q, J 7.0Hz), 7.05(1H, t, J 7.0Hz), 6.88-6.83(1H, m) and 5.75(2H, s). 58 B 15 mp 207.0-207.4° C.; IRν_(max)(Nujol)/cm⁻¹ 3496, 3229, 3201, 3057, 2965, 2743, 1785 and 1615;NMR δ_(H)(400MHz, DMSO) 8.13-8.10(1H, m), 7.89(1H, d, J 3.5Hz),7.40-7.27(4H, m), 7.08(1H, dt, J 8.5, 3.0Hz), 6.87-6.84(1H, m) and5.66(2H, s). 59 B 30 mp 187.9-188.7° C. IRν_(max)(DR)/cm⁻¹ 3338, 3202,1659, 1607, 1567, 1523, 1457, 1424, 1321, 1204 and 1025; NMRδ_(H)(400MHz, DMSO) 7.88(1H, d, J 3.5Hz), 7.65(1H, t, J 7.5Hz), 7.29(2H,br s), 7.18(1H, d, J 7.5Hz), 6.89(1H, d, J 8.0Hz), 6.51(1H, d, J 3.0Hz),5.69(2H, s), 2.46(3H, s) and 2.42(3H, s); Anal. Calcd for C₁₆H₁₅N₇O.0.2H₂O: C, 59.14; H, 4.78, N, 30.17. Found: C, 59.37; H, 4.66; N, 29.86. 60B 33 mp 209.7-209.8° C.; IR ν_(max)(DR)/cm⁻¹ 3404, 3330, 3226, 3109,2961, 2926, 2742, 1637, 1601, 1508, and 1474; NMR δ_(H)(400MHz, DMSO)7.83(1H, dd, J 0.5, 3.2Hz), 7.54-7.46(1H, m), 7.3(2H, br s), 7.16(2H, t,J 8.2Hz), 6.49(1H, dd, J 1.0, 3.5Hz), 5.63(2H, s) and 2.44(3H, s). 61 B20 mp 193.8-194.1° C.; IR ν_(max)(DR)/cm⁻¹ 3336, 3218, 2980, 2753, 2432,1734, 1654, 1611, 1438, 1381, 1331 and 1224; NMR δ_(H)(400MHz, DMSO)7.86(1H, d, J 3.0Hz), 7.49(1H, dd, J 1.5, 5.0Hz), 7.3(2H, br s),7.16(1H, dd, J 1.0, 3.5Hz), 7.0(1H, dd, J3.5, 5.0Hz), 6.50(1H, dd, J1.0, 3.5Hz), 5.82(2H, s) and 2.45(3H, s). 62 B 40 mp 210.4-210.5° C.; IRν_(max)(DR)/cm⁻¹ 3511, 3300, 3179, 2940, 2740, 2688, 1986, 1832, 1734,1634, 1500 and 1436; NMR δ_(H)(400MHz, DMSO) 7.87(1H, d, J 3.5Hz),7.40-7.37(3H, m), 7.30(2H, br s), 7.23-7.18(1H, m), 6.51 (1H, dd, J 1.0,5.1Hz), 5.68(2H, s) and 2.45(3H, s). 63 N 41 mp 201.1-201.2° C.; IRν_(max)(DR)/cm⁻¹ 3453, 3317, 3195, 1638, 1599, 1510, 1434; NMRδ_(H)(400MHz, DMSO) 8.28(1H, d, J 6.0Hz), 8.12-8.11(1H, m), 7.91(1H, d,J 3.5Hz), 7.29(2H, br s), 6.91(1H, dd, J 6.0, 2.5Hz), 6.87-6.85 (2H, m),5.71(2H, s), 3.81(3H, s). 64 B 9 mp 218.0-218.1° C.; IR ν_(max)(DR)/cm⁻¹3999, 3376, 3209, 2916, 2747, 2326, 1957, 1782, 1610, 1515, 1278, 1023and 763; NMR δ_(H)(400MHz, DMSO) 2.42 (3H, s), 5.64(2H, s), 6.86(1H, s),6.91(1H, d, J 7.5Hz), 7.13(1H, t, J 7.0Hz), 7.17-7.26(2H, m), 7.32(2H,s), 7.90(1H, d, J 3.5Hz), 8.12(1H, s). 65 B 25 mp 208.1-208.2° C.; IRν_(max)(Nujol)/cm⁻¹ 3347, 3199, 2981, 2932, 2764, 2719, 1660 and 1612;NMR δ_(H)(400MHz, DMSO) 8.14-8.11(1H, m), 7.90(1H, d, J 3.5Hz),7.41-7.22(4H, m), 7.15-7.09(1H, m), 6.87-6.83(1H, m) and 5.69 (2H, s);Anal. Calcd for C₁₅H₁₀F₂N₆O.0.5 H₂O: C, 53.42; H, 3.29, N, 24.92. Found:C, 53.72; H, 3.06; N, 24.77. 66 W 25 mp 243.4-243.9° C.; IRν_(max)(Nujol)/cm⁻¹ 4008, 3483, 3316, 3196, 1734, 1599 and 1505; NMRδ_(H)(400MHz, DMSO) 8.32(1H, dd, J 9.0, 3.0Hz), 8.21(1H, d, J 3.0Hz),8.12-8.10(1H, m), 7.68(1H, d, J 3.5Hz), 7.31(1H, d, J 9.0Hz), 7.00(2H,s), 6.85-6.82(1H, m), 5.94(2H, s) and 3.93(3H, s); Anal. Calcd forC₁₆H₁₃N₇O₄: C, 52.32; H, 3.57, N, 26.68. Found: C, 52.16; H, 3.56; N,26.67. 67 B 32 mp 252.9-253.0° C.; IR ν_(max)(DR)/cm⁻¹ 3511, 33260,2945, 1732, 1626, 1573, 1499, 1422, 1327 and 1222; NMR δ_(H)(400MHz,DMSO) 8.4(1H, d, J 4.5Hz), 7.87(1H, d, J 3.0Hz), 7.77-7.71(2H, m)7.47-7.38(2H, m), 7.3(2H, br s), 6.50(1H, dd, J 1.0, 3.5Hz), 5.70(2H,s), 2.75(3H, d, J 4.5Hz) and 2.45(3H, s). 68 R 58 mp 228.1-229.3° C.; IRν_(max)(Nujol)/cm⁻¹ 3508, 3263, 2990, 2946, 2837, 1646 and 1419; NMRδ_(H)(400MHz, DMSO) 8.29(1H, t, J 6.0Hz), 8.14-8.09(1H, m), 7.90(1H, d,J 3.5Hz), 7.33(2H, s), 7.29(1H, t, J 7.5Hz), 7.21-7.09(3H, m),6.88-6.83(1H, m), 5.64(2H, s), 4.20(1H, d, J 6.0Hz) and 1.83(3H, s);Anal. Calcd for C₁₈H₁₇N₇O₂.0.25 H₂O: C, 58.77; H, 4.79, N, 26.65. Found:C, 58.86; H, 4.54; N, 26.24. 69 X 2 NMR δ_(H)(400MHz, DMSO) 8.53(1H, s),7.69(1H, s), 7.58(2H, br s), 7.45-7.36 (1H, m), 7.29-7.22(2H, m),7.21-7.15(1H, m) and 5.73(2H, s); Retention time 1.14 min. 70 N 39 NMRδ_(H)(400MHz, DMSO) 8.45(1H, d, J 5.0, 1.0Hz), 8.13-8.12(1H, m),7.91(1H, dd, J 3.5, 1.0Hz), 7.51-7.48(2H, m), 7.31(2H, br s),6.87-6.85(1H, m), 5.80(2H, s); Retention time 1.75 min. 71 N 65 mp228.7-228.9° C.; IR ν_(max)(DR)/cm⁻¹ 3408, 3326, 3210, 1648, 1614, 1511;NMR δ_(H)(400MHz, DMSO) 8.13-8.12(1H, m), 8.02-7.96(1H, m), 7.92(1H, d,J 3.5Hz), 7.33(2H, br s), 7.20(1H, dd, J 7.5, 2.0Hz), 7.12(1H, dd, J8.0, 2.0Hz), 6.87(1H, dd, J 3.5, 1.0Hz), 5.75(2H, s); Anal. Calcd forC₁₄H₁₁N₇OF.0.2 H₂O.0.1 C₄H₁₀O₂: C, 53.66; H, 3.57, N, 30.42. Found: C,53.68; H, 3.44; N, 30.24. 72 B 28 mp 195.4-196.5° C.; IRν_(max)(DR)/cm⁻¹ 3328, 3210, 2956, 2836, 2740, 1736, 1648, 1608, 1438,1322 and 1250; NMR δ_(H)(400MHz, DMSO) 7.87(1H, d, J 3.5Hz),7.33-7.25(3H, m), 7.05(1H, d, J 7.5Hz), 6.88(1H, td, J 1.0, 7.5Hz),6.87(1H, dd, J 2.0, 7.5Hz), 6.50(1H, dd, J 1.0, 3.5Hz), 5.58(2H, s),3.83(3H, s) and 2.45(3H, s). 73 B 28 mp 178.7-179.3° C.; IRν_(max)(DR)/cm⁻¹ 3468, 3346, 3172, 2988, 2747, 2130, 1943, 1696, 1610,1418, 1330, and 1177; NMR δ_(H)(400MHz, DMSO) 7.86(1H, d, J 3.01Hz),7.34-7.26(4H, m), 7.20-7.10(2H, m) 7.09(1H, s), 6.50(1H, dd, J 1.0,3.5Hz), 5.63(2H, s), 4.2(2H, d, J 6.0Hz), 2.45(2H, s) and 1.34(9H, s).74 C 40 mp 214.6-215.2° C.; IR ν_(max)(DR)/cm⁻¹ 2877, 1653, 1596, 1523,1470, 1355, 1284, 1241, 1210 and 1109; NMR δ_(H)(400MHz, DMSO) 7.87(1H,d, J 3.0Hz), 7.16(1H, t, J 7.0Hz), 7.0-6.75(3H, m), 6.51(1H, d, J3.0Hz), 5.58(2H, s) and 2.45(3H, s). 75 C 3 NMR δ_(H)(400MHz, DMSO)4.74(4H, s), 5.33(2H, s), 5.62(2H, d, J 2.0Hz), 5.71(1H, t, J 2.0Hz),6.83-6.88(1H, m), 7.29(2H, s), 7.91(1H, dd, J 3.5, 1.0Hz), 8.10-8.12(1H,m); Retention time 2.95 min. 76 K 100 IR ν_(max)(DR)/cm⁻¹ 3011, 1650,1525, 1468, 1351, 1284 and 1210; NMR δ_(H)(400MHz, CD₃OD) 8.36(1H, d, J3.5Hz), 7.53-7.42(4H, m), 6.72(1H, dd, J 1.0Hz, 3.5Hz), 5.76(2H, s),4.11(2H, s) and 2.61(3H, s). 77 W 25 mp 212.1-214.3° C.; IRν_(max)(DR)/cm⁻¹ 4007, 3474, 3323, 3199, 2934, 2747, 2105, 1647, 1603,1492, 1245, 1028 and 754; NMR δ_(H)(400MHz, DMSO) 3.82 (3H, s), 5.60(2H,s), 6.78-6.93(3H, m), 7.05(1H, d, J 8.5Hz), 7.24-7.38 (3H, m), 7.90(1H,d, J 3.0Hz), 8.12(1H, s). 78 B 21 IR ν_(max)(DR)/cm⁻¹ 4002, 3482, 3313,3201, 2938, 2739, 2339, 2107, 1936, 1731, 1650, 1436, 1253, 1082 and751; NMR δ_(H)(400MHz, DMSO) 5.82(2H, s), 6.84-6.88 (1H, m), 7.38(2H,s), 7.58(1H, t, J 9.0Hz), 7.90(1H, t, J 3.0Hz), 8.12 (1H, d, J 1.0Hz),8.23-8.28(1H, m), 8.29-8.35(1H, m). 79 C 64 mp 308.2-308.3° C.; IRν_(max)(DR)/cm⁻¹ 4013, 3456, 3322, 3193, 2958, 2745, 2103, 1861, 1653,1516, 1237, 1026 and 777; NMR δ_(H)(400MHz, DMSO) 4.95 (2H, s), 5.56(2H,s), 6.15-6.20(1H, m), 6.44-6.51(1H, m), 6.84-6.93(2H, m), 7.34(2H, s),7.91(1H, d, J 3.0Hz), 8.12(1H, d, J 1.0Hz). 80 Y 10 NMR δ_(H)(400MHz,DMSO) 8.84(1H, br s), 7.46-7.35(2H, m), 7.32-7.14 (4H, m) and 5.72(2H,s); Retention time 0.84 min. 81 B 47 mp 229.3-229.4° C.; IRν_(max)(DR)/cm⁻¹ 3514, 3292, 3166, 1614, 1503; NMR δ_(H) (400MHz, DMSO)7.88-7.84(2H, m), 7.47(1H, d, J 8.0Hz), 7.31(2H, br s), 7.22(1H, d, J7.0Hz), 6.52-6.51(1H, m), 5.75(2H, s), 2.46(3H, s); Anal. Calcd forC₁₅H₁₂N₇OCl.0.1 H₂O: C, 52.44; H, 3.58, N, 28.54. Found: C, 52.62; H,3.59; N, 28.20. 82 H 36 mp 205.0-205.3° C.; NMR δ_(H)(400MHz, DMSO)7.97-7.85(5H, m), 7.46-7.41 (3H, m), 7.32(2H, br s), 7.13(1H, d, J8.5Hz), 6.53-6.52(1H, m), 5.85 (2H, s), 2.46(3H, s). 83 C 19 mp252.8-253.3° C.; NMR δ_(H)(400MHz, MeOD) 8.21(1H, d, J 3.0Hz), 7.98 (1H,d, 3.5Hz), 7.62-7.52(2H, m), 7.37-7.31(2H, m) and 5.81(2H, s); Retentiontime 0.83 min. 84 C 53 mp 235.8-236.5° C.; IR ν_(max)(DR)/cm⁻¹ 3309,2836, 2033, 1823, 1651, 1505, 1468, 1354, 1250 and 1209; NMRδ_(H)(400MHz, CD₃OD) 8.18(1H, d, J 4.0Hz), 7.47-7.37(3H, m), 6.61(1H,dd, J 1.0, 3.5Hz), 5.82(2H, s) and 2.57(3H, s). 85 R 72 mp 215.9-217.5°C.; IR ν_(max)(Nujol)/cm⁻¹ 3308, 2955, 2869, 1634, 1505 and 1435; NMRδ_(H)(400MHz, DMSO) 8.27(1H, t, J 5.5Hz), 8.13(1H, d, J 1.0Hz), 7.91(1H,d, J 3.5Hz), 7.36(2H, s), 7.31(1H, t, J 7.5Hz), 7.17(2H, t, J 7.5Hz),7.09(1H, s), 6.89-6.84(1H, m), 5.64(2H, s), 4.21(2H, d, J 6.0Hz),1.93(2H, s) and 0.79(6H, d, J 6.5Hz). 86 B 51 NMR δ_(H)(400MHz, DMSO)8.84(1H, d, J 5.5Hz), 8.14(1H, d, J 2.0Hz), 8.08 (1H, dd, J 5.5, 1.0Hz),7.89(1H, d, J 5.5Hz), 7.34(2H, br s), 6.53-6.52(1H, m), 5.98(2H, s),2.46(3H, s); Retention time 1.85 min. 87 Z 73 NMR δ_(H)(400MHz, DMSO)9.10(1H, s), 8.69(1H, s), 8.05(1H, d, J 5.5Hz), 7.89(1H, d, J 3.0Hz),7.32(2H, br s), 6.59-6.57(1H, m), 6.53-6.51(1H, m), 6.37-6.36(1H, m),5.60(2H, s), 2.46(3H, s); M/Z 339(M+H)⁺; Retention time 0.79 min. 88 B11 mp 258.8-259.0° C.; IR ν_(max)(DR)/cm⁻¹ 4014, 3316, 3204, 2966, 2746,2561, 2106, 1962, 1606, 1526, 1436, 1351, 1029 and 758; NMRδ_(H)(400MHz, DMSO) 2.46(3H, s), 5.79(2H, s), 6.86-6.88(1H, m), 7.23(1H,d, J 7.5Hz), 7.30-7.50 (3H, m), 7.81(1H, d, J 8.0Hz), 7.91(1H, d, J3.5Hz), 8.13-8.15(1H, m). Anal. Calcd for C₁₆H₁₃N₇O₃: C, 54.70; H, 3.73;N, 27.89. Found: C, 54.70; H, 3.77; N, 27.48. 89 C 57 mp 247.1-247.2°C.; IR ν_(max)(DR)/cm⁻¹ 3322, 1740, 1600, 1240, 1167, 959 and 770; NMRδ_(H)(400MHz, DMSO) 2.10(3H, s), 4.93(2H, s), 5.56(2H, s), 6.11 (1H, d,J 6.5Hz), 6.58(1H, d, J 8.0Hz), 6.80(1H, t, J 7.5Hz), 6.85-6.87(1H, m),7.35(2H, s), 7.90(1H, d, J 3.5Hz), 8.12-8.14(1H, m). 90 C 38 mp268.5-269.1° C.; IR ν_(max)(DR)/cm⁻¹ 4010, 3451, 3317, 3182, 2957, 2749,2104, 1844, 1652, 1608, 1487, 1335, 1025 and 764; NMR δ_(H)(400MHz,DMSO) 1.99(3H, s), 4.89(2H, s), 5.47(2H, s), 6.36-6.43(2H, m),6.84-6.89(2H, m), 7.35(2H, s), 7.91(1H, d, J 3.5Hz) 8.12-8.14(1H, m). 91B 15 mp 284.3-284.5° C.; IR ν_(max)(DR)/cm⁻¹ 3321, 3216, 1612, 1031, 765and 552; NMR δ_(H)(400MHz, DMSO) 8.12(1H, d, J 1.0Hz), 7.88(1H, d, J3.5Hz), 7.35 (2H, br s), 6.85(1H, dd, J 3.5, 1.5Hz), 5.44(2H, s),2.52(3H, s) and 2.25(3H, s) 92 B 8 mp 267.9-268.5° C.; NMR δ_(H)(400MHz,DMSO) 2.32(3H, s), 5.69(2H, s), 6.85-6.89(1H, s), 7.04-7.10(1H, m),7.33-7.54(4H, m), 7.90(1H, d, J 3.5Hz), 8.13-8.15(1H, m). 93 B 4 IRν_(max)(Nujol)/cm⁻¹ 3316, 3193, 2926, 2851, 1637, 1508 and 1437; NMRδ_(H) (400MHz, DMSO) 8.11-8.09(1H, m), 7.89(1H, dd, J 3.5, 1.0Hz),7.27(2H, s), 6.86-6.83(1H, m), 4.26(2H, d, J 7.5Hz), 2.04-1.90(1H, m),1.72-1.50 (5H, m) and 1.25-0.95(5H, m). 94 B 15 mp 237.8-238.0° C.; NMRδ_(H)(400MHz, DMSO) 2.49(3H, s), 5.76(2H, s), 6.84-6.88(1H, m), 7.28(1H,dd, J 8.5, 1.5Hz), 7.30-7.42(3H, m), 7.91(1H, d, J 3.5Hz), 7.97(1H, d, J8.5Hz), 8.11-8.14(1H, m). Anal. Calcd for C₁₆H₁₃N₇O₃.0.1 H₂O: C, 54.42;H, 3.77; N, 27.77. Found: C, 54.73; H, 3.78; N, 27.40. 95 N 32 mp249.8-250.0° C.; IR ν_(max)(DR)/cm⁻¹ 3437, 3317, 3210, 2964, 2865, 1610,1508; NMR δ_(H)(400MHz, DMSO) 8.19-8.17(1H, m), 8.12(1H, m), 7.92-7.91(1H, m), 7.66-7.63(1H, m), 7.24-7.20(3H, m), 6.86(1H, dd, J 3.5, 1.5Hz),5.80(2H, s), 2.44(3H, s). 96 B 4 mp 226.6-226.9° C.; NMR δ_(H)(400MHz,DMSO) 2.32(3H, s), 5.98(2H, s), 6.84(1H, s), 6.85-6.90(1H, m), 7.35(2H,s), 7.43(1H, d, J 7.5Hz), 7.91(1H, d, J 7.5Hz), 8.07-8.15(2H, m). 97 C63 mp 245.3-246.1° C.; IR ν_(max)(DR)/cm⁻¹ 4010, 3406, 3320, 3198, 2929,2746, 1608, 1507, 1414, 1285, 1022 and 753; NMR δ_(H)(400MHz, DMSO)2.00(3H, s), 4.86(2H, s), 5.42(2H, s), 6.54(1H, d, J 8.0Hz),6.82-6.85(1H, m), 6.90 (1H, dd, J 8.0, 2.0Hz), 6.92-6.95(1H, m),7.29(2H, s), 7.88(1H, d, J 3.5Hz), 8.09-8.12(1H, m). Anal. Calcd forC₁₆H₁₅N₇O.0.2 H₂O: C, 59.14; H, 4.78; N, 30.17. Found: C, 59.44; H,4.74; N, 29.82. 98 O 98 IR ν_(max)(Nujol)/cm⁻¹ 3324, 3206, 1698, 1650and 1611; NMR δ_(H)(400MHz, DMSO) 13.56-12.46(1H, s), 8.13-8.11(1H, s),7.92-7.84(3H, m), 7.56-7.31 (3H, m), 6.87-6.85(1H, m) and 7.74(2H, s).99 P 66 IR ν_(max)(Nujol)/cm⁻¹ 3324, 1644, 1491 and 1417; NMRδ_(H)(400MHz, DMSO) 8.12(1H, s), 7.98-7.93(1H, s), 7.91(1H, d, J 3.0Hz),7.81(1H, d, J 6.5Hz), 7.77(1H, s), 7.47-7.29(5H, m), 6.86(1H, s) and5.77-5.68(2H, m). 100 B 13 mp 285.7-285.9° C.; IR ν_(max)(DR)/cm⁻¹ 3345,3197, 1664, 1613, 1116, 766 and 600; NMR δ_(H)(400MHz, DMSO)8.13-8.02(1H, m) 7.90(1H, d, J 3.5Hz), 7.37-7.27(3H, m), 6.86(1H, dd, J3.5, 2.0Hz), 5.67(2H, s) and 2.52(3H, s). 101 AA 32 mp 279.9-280.3° C.;NMR δ_(H)(400MHz, DMSO) 8.33(3H, br s), 7.93(1H, d, J 2.0Hz),7.51-7.39(2H, m), 7.39-7.31(3H, m), 5.69(2H, s) and 3.98(2H, q, J5.5Hz). 102 P 23 IR ν_(max)(Nujol)/cm⁻¹ 3480, 3322, 3202, 283, 1608 and1506; NMR δ_(H)(400MHz, DMSO) 8.12(1H, s), 7.90(1H, d, J 3.5Hz),7.47-7.25(5H, m), 6.87-6.84 (1H, m), 5.72(2H, s), 3.77-3.61(1H, s),2.76(3H, s), 1.10(3H, s) and 0.99 (3H, s). 103 P 58 IRν_(max)(Nujol)/cm⁻¹ 3298, 2972, 1635 and 1418; NMR δ_(H)(400MHz, DMSO)8.21(1H, d, J 7.5Hz), 8.12(1H, s), 7.91(1H, d, J 3.0Hz), 7.82-7.74(2H,m), 7.48-7.29(4H, m), 6.86(1H, s), 5.71(2H, s), 4.13-4.01(1H, m) and1.13(6H, d, J 6.5Hz). 104 C 10 mp 249.9-250.5° C.; NMR δ_(H)(400MHz,DMSO) 2.07(3H, s), 5.06(2H, s), 5.43(2H, s), 6.60-6.65(2H, m),6.81-6.89(2H, m), 7.37(2H, s), 7.90(1H, dd, J 3.5, 1.0Hz), 8.12(1H, d, J1.0Hz). Anal. Calcd for C₁₆H₁₅N₇O.0.2H₂O: C, 59.14; H, 4.78; N, 30.17.Found: C, 59.53; H, 4.75; N, 29.87. 105 B 16 mp 263.2-263.5° C.; IRν_(max)(DR)/cm⁻¹ 3499, 3307, 3192, 2958, 2238, 1610, 1490; NMRδ_(H)(400MHz, DMSO) 8.73(1H, d, J 5.0Hz), 8.13-8.12(1H, m),7.92-7.90(1H, m), 7.85-7.81(2H, m), 7.30(2H, br s), 6.87-6.86(1H, m),5.87(2H, s). 106 B 16 mp 288.1-288.2° C.; IR ν_(max)(DR)/cm⁻¹ 3324,3196, 1609, 1489, 1166, 1004, 798 and 550; NMR δ_(H)(400MHz, DMSO)8.59(1H, s), 8.44(1H, s), 8.12(1H, s), 7.90(1H, d, J 3.5Hz), 7.31(2H, brs), 6.86(1H, dd, J 3.5, 1.5Hz), 5.81(2H, s) and 2.48(3H, s). 107 B 22 mp276.4-277.4° C.; IR ν_(max)(DR)/cm⁻¹ 3443, 3324, 3202, 1610, 1324, 1229,1030 and 788; NMR δ_(H)(400MHz, DMSO) 9.01(1H, dd, J 4.0, 2.0Hz),8.45(1H, dd, J 8.5, 2.0Hz), 8.14-8.12(1H, m), 7.97(1H, d, J 8.0Hz),7.93(1H, d, J 3.5Hz), 7.64(1H, 1H, dd, J 8.5, 4.0Hz), 7.52(1H, t, J7.0Hz), 7.31(2H, br s), 7.15(1H, d, J 7.5Hz), 6.87(1H, dd, J 3.5, 2.0Hz)and 6.31(2H, s). 108 B 30 mp 215.0-215.3° C.; IR ν_(max)(DR)/cm⁻¹ 3325,3198, 1612, 1246, 1026, 727 and 567; NMR δ_(H)(400MHz, DMSO)8.14-8.12(1H, m), 7.91(1H, dd, J 3.5, 1.0Hz), 7.90-7.85(2H, m), 7.52(1H,s), 7.51-7.46(3H, m), 7.36(2H, br s), 6.86 (1H, dd, J 3.5, 1.5Hz), and5.81(2H, s). 109 Q 23 mp 289.8-289.9° C.; IR ν_(max)(DR)/cm⁻¹ 3350,2924, 2863, 1981, 1723, 1618, 1351, 1100, 974, 766 and 524; NMRδ_(H)(400MHz, DMSO) 8.23-8.16(2H, m), 7.77-7.62(3H, m), 7.49(2H, br s),5.88(2H, s) and 2.56(3H, s). 110 B 31 mp 247.4-247.5° C.; IRν_(max)(DR)/cm⁻¹ 3999, 3470, 3316, 3198, 2929, 2744, 2345, 2103, 1924,1837, 1773, 1649, 1435, 1355, 1237, 1029 and 768; NMR δ_(H) (400MHz,DMSO) 5.79(2H, s), 6.85-6.87(1H, m), 7.36(2H, s), 7.56(1H, dd, J 8.5,2.0Hz), 7.76(1H, d, J 8.0Hz), 7.91(1H, dd, J 3.5, 1.0Hz), 8.04(1H, d, J2.0Hz), 8.12-8.13(1H, m). Anal. Calcd for C₁₅H₁₀N₇O₃Cl: C, 48.47; H,2.71; N, 26.36. Found: C, 48.63; H, 2.80; N, 26.22. 111 B 14 mp244.1-244.6° C.; NMR δ_(H)(400MHz, DMSO) 5.84(2H, s), 6.85-6.89 (1H, m),7.37(2H, s), 7.54(1H, dd, J 9.5, 1.5Hz), 7.84(1H, t, J 1.0Hz), 7.92 (1H,d, J 3.5Hz), 8.08(1H, dd, J 9.0, 1.0Hz), 8.12-8.15(1H, m). Anal. Calcdfor C₁₅H₁₀N₈O₂.0.75 C₃H₇NO: C, 53.25; H, 3.95; N, 31.50. Found: C,53.08; H, 3.79; N, 31.38. 112 B 28 mp 190.4-191.4° C.; IRν_(max)(DR)/cm⁻¹ 3482, 3308, 3194, 2940, 2880, 1610, 1508; NMRδ_(H)(400MHz, DMSO) 8.13-8.12(1H, m), 7.92(1H, d, J 3.5Hz), 7.78(1H, t,J 8.0Hz), 7.35-7.32(3H, m), 7.04(1H, d, J 7.5Hz), 6.86(1H, dd, J 3.5,2.0Hz), 5.75(2H, s), 4.43(2H, s), 3.33(3H, s). 113 B 39 IRν_(max)(Nujol) cm⁻¹ 3499, 3316, 3193, 2946, 1651 and 1509; NMRδ_(H)(400MHz, DMSO) 8.13-8.10(1H, m), 7.90(1H, d, J3.5Hz), 7.39-7.26(7H,m), 6.87-6.84(1H, m) and 5.67(2H, s); Anal. Calcd for C₁₅H₁₂N₆O.0.75H₂O: C, 58.91; H, 4.45, N, 27.48. Found: C, 58.84; H, 4.10; N, 27.32.114 C 67 mp 256.7-257.1° C.; IR ν_(max)(DR)/cm⁻¹ 4003, 3452, 3324, 3203,2950, 2746, 2102, 1733, 1654, 1516, 1420, 1305, 1221, 1106, 1024 and761; NMR δ_(H)(400MHz, DMSO) 5.38(2H, s), 5.51(2H, s), 6.46(1H, dd, J8.5, 2.5Hz), 6.58(1H, d, J 2.0Hz), 6.84-6.87(1H, m), 7.15(1H, d, J8.0Hz), 7.32(2H, s), 7.91(1H, dd, J 3.5, 1.0Hz), 8.11-8.13(1H, m). Anal.Calcd for C₁₅H₁₂N₇OCl.0.3 H₂O: C, 51.90; H, 3.66; N, 28.24. Found: C,52.12; H, 3.48; N, 27.86. 115 B 12 NMR δ_(H)(400MHz, DMSO) 8.84(1H, d, J5.5Hz), 8.15-8.12(2H, m), 8.08-8.06 (1H, m), 7.92-7.91(1H, m), 7.32(2H,br s), 6.87(1H, dd, J 3.5, 1.5Hz), 5.99(2H, s); Retention time 1.28 min.116 Z 87 NMR δ_(H)(400MHz, DMSO) 9.08(1H, br s), 8.66(1H, br s),8.13-8.12(1H, m), 8.06-8.04(1H, m), 7.93-7.91(1H, m), 7.32(2H, br s),6.87-6.86(1H, m), 6.60-6.58(1H, m), 6.38-6.37(1H, m), 5.61(2H, s); M/Z325(M+H)⁺. 117 B 9 IR ν_(max)(DR)/cm⁻¹ 3491, 3310, 3198, 2976, 1612; NMRδ_(H)(400MHz, DMSO) 8.14-8.13(1H, m), 7.99-7.98(1H, m), 7.93-7.91(1H,m), 7.80-7.79(1H, m), 7.34(2H, br s), 6.88-6.86(1H, m), 5.90(2H, s),2.57(3H, s). 118 Z 91 NMR δ_(H)(400MHz, DMSO) 13.45(1H, br s), 9.50(1H,br s), 8.15-8.14(1H, m), 7.92(1H, d, J 3.5Hz), 7.39(2H, br s),6.87-6.86(1H, m), 6.56(1H, br s), 6.15(1H, br s), 5.67(2H, s), 2.39(3H,s); M/Z 339(M+H)⁺. 119 B 15 mp > 230° C.; IR ν_(max)(DR)/cm⁻¹ 3993,3509, 3314, 3195, 2997, 2950, 2682, 2561, 2101, 1943, 1780, 1613, 1501,1433, 1345, 1100, 1027, 889 and 780; NMR δ_(H)(400MHz, DMSO) 6.00(2H,s), 6.85-6.90(1H, m), 7.05(1H, d, J 8.5Hz), 7.37(2H, s), 7.78(1H, dd, J8.5, 2.0Hz), 7.91(1H, d, J 3.5Hz), 8.14(1H, d, J 1.0Hz), 8.27(1H, d, J2.5Hz). Anal. Calcd for C₁₅H₁₀N₇O₃Cl.0.3 H₂O: C, 47.77; H, 2.83; N,26.00. Found: C, 47.65; H, 2.71; N, 25.85. 120 C 19 mp 211.4-211.6° C.;IR ν_(max)(DR)/cm⁻¹ 4015, 3325, 3218, 2969, 2878, 2101, 1653, 1508,1423, 1275, 1023, 834 and 761; NMR δ_(H)(400MHz, DMSO) 5.45 (2H, s),5.60(2H, s), 6.51(1H, dd, J 8.0, 2.0Hz), 6.70-6.79(2H, m), 6.83-6.89(1H, m), 7.38(2H, s), 7.90(1H, d, J 3.5Hz), 8.12(1H, s). 121 B 13 mp292.3-292.4° C.; IR ν_(max)(DR)/cm⁻¹ 3324, 3207, 2098, 1602, 1527, 1352,1024 and 813; NMR δ_(H)(400MHz, CDCl3) 8.10(1H, d, J 3.0Hz), 7.79(1H, d,J 1.5Hz), 7.64(2H, d, J 8.5Hz), 7.49(2H, d, J 8.5Hz), 6.71(1H, dd, J3.5, 1.5Hz), 5.71(2H, s) and 5.38(2H, br s). 122 A 50 mp 227.5-228.5°C.; IR ν_(max)(DR)/cm⁻¹, 3265, 1701, 1521, 1480, 1413, 1355, 1309, 1204and 1147; NMR δ_(H)(400MHz, DMSO) 8.11(1H, d, J 1.0Hz), 7.9( 1H, d, J3.5Hz), 7.3(2H, br s), 7.04(1H, d, J 2.0Hz), 6.90( 1H, d, J 8.0Hz),6.85(1H, dd, J 1.5, 3.5Hz), 6.79(1H, dd, J 2.0, 8.0Hz), 5.57(2H, s),3.71(3H, s,) and 3.72(3H, s). 123 B 35 mp 214.6-216.2° C.; IRν_(max)(DR)/cm⁻¹ 3512, 3295, 3173, 2988, 2736, 2415, 1636, 1437, 1340and 1228; NMR δ_(H)(400MHz, DMSO) 7.97(1H, d, J 8.5Hz), 7.87(1H, d, J3.0Hz), 7.40(1H, d, J 1.0Hz), 7.31(2H, br s), 7.27(1H, dd, J 1.5,8.0Hz), 6.51(1H, dd, J 1.0, 3.5Hz), 5.74(2H, s), 2.48(3H, s) and2.46(3H, s). 124 C 65 mp 215.7-216.7° C.; IR ν_(max)(DR)/cm⁻¹ 3328,2928, 2424, 2345, 1609 and 1263; NMR δ_(H)(400MHz, DMSO) 7.85(1H, d, J3.5Hz), 7.26(2H, br s), 6.93(1H, d, J 1.5Hz), 6.89(1H, dd, J 2.0,8.0Hz), 6.54(1H, d, J 8.0Hz), 6.49(1H, J 1.0, 3.5Hz), 5.40(2H, s),4.89(2H, br s), 2.45(3H, s) and 2.27(3H, s). 125 B 29 mp 221.5-221.6°C.; IR ν_(max)(DR)/cm⁻¹ 3506, 3294, 3178, 2683, 1613, 1315, 1027 and697; NMR δ_(H)(400MHz, DMSO) 8.13-8.11(1H, m), 7.90(1H, d, J 4.5Hz),7.38(2H, br s), 6.86(1H, dd, J 3.5, 1.5Hz), 6.18-6.16(1H, m), 5.70 (2H,s) and 2.36(3H, s). 126 N 26 mp 229.6-230.3° C.; IR ν_(max)(DR)/cm⁻¹3317, 3198, 1602, 1499; NMR δ_(H)(400MHz, DMSO) 8.44-8.43(1H, m),8.31(1H, d, J 5.0Hz), 8.14-8.13(1H, m), 7.92(1H, d, J 3.0Hz), 7.35(2H,br s), 6.88-6.86(1H, m), 6.70(1H, d, J 5.0Hz), 5.71(2H, s), 2.39(3H, s).127 B 13 mp 275.0-273.3° C.; IR ν_(max)(DR)/cm⁻¹ 3449, 3310, 3202, 1605,1487, 1420, 1023, 836, 760 and 551; NMR δ_(H)(400MHz, DMSO)8.15-8.11(1H, m), 8.07 (1H, d, J 9.0Hz), 7.91(1H, d, J 3.5Hz), 7.68(1H,dd, J 9.0, 6.5Hz), 7.38-7.29 (3H, m), 6.86(1H, dd, J 3.5, 1.5Hz) and6.15(2H, s). 128 B 16 mp 129.1-131.0° C.; IR ν_(max)(DR)/cm⁻¹ 3993,3470, 3310, 3197, 1610, 1508, 1420, 1239, 1002 and 796; NMRδ_(H)(400MHz, DMSO) 8.74(1H, d, J 1.5Hz), 8.61(1H, d, J 2.5Hz),8.57-8.54(1H, m), 8.13-8.11(1H, m), 7.91(1H, d, J 3.5Hz), 7.31(2H, brs), 6.86(1H, dd, J 3.5, 2.0Hz) and 5.88(2H, s). 129 B 20 mp 266.5-266.7°C.; IR ν_(max)(DR)/cm⁻¹ 4018, 3487, 3310, 3193, 2744, 1636, 1585, 1539,1507, 1437, 1347, 1266, 1238 and 1196; NMR δ_(H)(400MHz, DMSO) 8.15(1H,dd, J 2.5, 7.5Hz), 8.12(1H, d, J 1.0Hz), 7.90( 1H, d, J 3.5Hz),7.73-7.68(1H, m), 7.58(1H, dd, J 11.3, 8.8Hz), 7.36(2H, br s), 6.88(1H,dd, J 1.5, 3.5Hz) and 5.78(2H, s). 130 H 32 mp 149.0-149.6° C.; IRν_(max)(DR)/cm⁻¹ 4072, 3332, 3198, 1654, 1604, 1348, 1237, 1111, 1012,775, 691 and 570; NMR δ_(H)(400MHz, DMSO) 8.79-8.70 (2H, m),8.25-8.14(2H, m), 7.77-7.58(5H, m), 7.38(2H, br s) and 5.87(2H, s). 131B 22 mp 225.7-225.8° C.; NMR δ_(H)(400MHz, DMSO) 8.33(1H, d, J 4.5Hz),8.13-8.12 (1H, m), 7.92-7.91(1H, m), 7.30(2H, br s), 7.15(1H, d, J5.0Hz), 7.07-7.06 (1H, m), 6.86(1H, dd, J 1.5, 3.5Hz), 5.72(2H, s),2.28(3H, s); Anal. Calcd for C₁₅H₁₃N₇O.0.7 H₂O: C, 56.31; H, 4.54, N,30.65. Found: C, 56.57; H, 4.24; N, 30.33. 132 N 10 IR ν_(max)(DR)/cm⁻¹3332, 2977, 1694, 1608; NMR δ_(H)(400MHz, DMSO) 8.41 (1H, d, J 4.5Hz),8.14-8.13(1H, m), 7.92(1H, d, J 3.5Hz), 7.43(1H, t, J 6.0Hz), 7.33(2H,br s), 7.16(1H, d, J 4.5Hz), 6.97-6.96(1H, m), 6.87(1H, dd, J 2.0,3.5Hz), 5.76(2H, s), 4.10(2H, d, J 6.0Hz), 1.31(9H, s). 133 B 14 mp209.7-209.9° C.; IR ν_(max)(Nujol)/cm⁻¹ 3506, 3311, 3196, 2996, 2951,1637, 1518 and 1283; NMR δ_(H)(400MHz, DMSO) 8.15-8.12(1H, m), 7.91(1H,dd, J 3.5, 1.0Hz), 7.84(1H, d, J 8.0Hz), 7.43(1H, d, J 1.5Hz),7.42-7.35(2H, s), 6.88-6.82(2H, m), 5.77(2H, s) and 3.91(3H, s). 134 B14 mp 240.9-241.1° C. IR ν_(max)(DR)/cm⁻¹ 4010, 3629, 3499, 3313, 3196,2946, 2733, 2447, 1943, 1638, 1528, 1420, 1351, 1222, 1025 and 960. NMRδ_(H)(400MHz, DMSO) 5.85(2H, s), 6.84-6.89(1H, m), 7.36(2H, s), 7.50(2H,dt, J 8.5, 2.0Hz), 7.92(1H, dd, J 3.5, 1.0Hz), 8.12-8.14(1H, m),8.22(2H, dt, J 9.0, 2.0Hz). Anal. Calcd for C₁₅H₁₁N₇O₃.0.6H₂O: C, 51.75;H, 3.53; N, 28.17. Found: C, 52.08; H, 3.22; N, 27.96. 135 B 18 mp208.6-208.8° C.; IR ν_(max)(DR)/cm⁻¹ 3432, 3304, 3191, 2961, 1616, 1500,1434; NMR δ_(H)(400MHz, DMSO) 8.14-8.13(1H, m), 7.93-7.91(1H, m), 7.67(1H, t, J 7.5Hz), 7.35(2H, br s), 7.19(1H, d, J 7.5Hz), 6.90-6.86(2H,m), 5.73 (2H, s), 2.68(2H, q, J 7.5Hz), 1.14(3H, t, J 7.5Hz). 136 B 18mp 172.7-173.2° C.; NMR δ_(H)(400MHz, DMSO) 8.42(1H, d, J 5.5Hz), 8.14(1H, m), 7.92(1H, d, J 3.5Hz), 7.39(2H, br s), 7.11-7.10(1H, m),6.97(1H, d, J 5.5Hz), 6.87(1H, dd, J 2.0, 3.5Hz), 5.70(2H, s), 2.71(2H,q, J 7.5Hz), 1.18 (3H, t, J 7.5Hz). 137 B 13 mp 176.3-176.5° C.; IRν_(max)(DR)/cm⁻¹ 3452, 3326, 3209, 2973, 1734, 1611, 1328, 1026 and 774;NMR δ_(H)(400MHz, DMSO) 8.13(1H, d, J 2.5Hz), 7.90 (1H, d, J 3.5Hz),7.72(1H, d, J 3.5Hz), 7.61(1H, d, J 8.5Hz), 7.34(2H, br s), 7.19(1H, t,J 8.0Hz), 6.86(1H, dd, J 3.5, 2.0Hz), 6.77(1H, d, J 4.0Hz), 6.75 (1H, d,J 7.5Hz), 6.07(2H, s) and 1.54(9H, s). 138 B 26 mp 58.5-62.6° C.; IRν_(max)(DR)/cm⁻¹ 3430, 3315, 3210, 3973, 1718, 1165, 834 and 772; NMRδ_(H)(400MHz, DMSO) 8.13-8.11(1H, m), 8.03(1H, d, J 8.0Hz), 7.89(1H, d,J 3.5Hz), 7.73(1H, d, J 4.0Hz), 7.39(2H, br s), 7.30(1H, t, J 8.5Hz),7.08(1H, d, J 7.0Hz), 6.91(1H, d, J 4.5Hz), 6.86(1H, dd, J 3.5, 1.5Hz),5.90(2H, s) and 1.62(9H, s). 139 K 85 mp 192.3-193.5° C.; NMRδ_(H)(400MHz, DMSO) 11.27(1H, br s), 8.12(1H, d, J 2.5Hz), 7.90(1H, d, J3.5Hz), 7.39-7.33(2H, m), 7.04(1H, t, J 8.0Hz), 6.87-6.83 (2H, m),6.56-6.52(1H, m) and 5.86(2H, s). 140 B 20 mp 184.0-185.2° C.; IRν_(max)(DR)/cm⁻¹ 3638, 3462, 3331, 3184, 2976, 1686, 1174, 1026 and 756;NMR δ_(H)(400MHz, DMSO) 8.13(1H, d, J 1.0Hz), 7.90 (1H, d, J 3.5Hz),7.45-7.31(3H, m), 7.27-7.17(4H, m), 6.86(1H, dd, J 3.5, 2.0Hz), 5.64(2H,s), 4.08(2H, d, J 6.0Hz) and 1.37(9H, s). 141 C 45 mp 240.3-240.4° C. IRν_(max)(DR)/cm⁻¹ 3320, 3198, 2929, 1610, 1505, 1438, 1280, 1233, 1028,956 and 759; NMR δ_(H)(400MHz, DMSO) 5.85(2H, s), 6.84-6.89 (1H, m),7.36(2H, s), 7.50(2H, dt, J 8.5, 2.0Hz), 7.92(1H, dd, J 3.5, 1.0Hz),8.12-8.14(1H, m), 8.22(2H, dt, J 9.0Hz). 142 B 14 mp 189.0-189.1° C.; IRν_(max)(DR)/cm⁻¹ 3506, 3304, 3180, 1735, 1609, 1167, 1029 and 766; NMRδ_(H)(400MHz, DMSO) 8.15-8.11(1H, m), 8.02(1H, d, J 8.5Hz), 7.91(1H, d,J 3.5Hz), 7.68(1H, d, J 3.5Hz), 7.53(1H, s), 7.37(2H, br s), 7.29(1H,dd, J 8.5, 1.5Hz), 6.86(1H, dd, J 3.5, 2.0Hz), 6.70(1H, d, J 3.5Hz),5.75(2H, s) and 1.61(9H, s). 143 B 18 mp 167.0-167.3° C.; IRν_(max)(DR)/cm⁻¹ 3650, 3485, 3320, 3194, 2978, 1726, 1168, 953 and 756;NMR δ_(H)(400MHz, DMSO) 9.00(1H, br s), 8.13(1H, s), 7.91(1H, d, J3.5Hz), 7.57(1H, t, J 8.0Hz), 7.39(2H, br s), 7.16(1H, d, J 11.5Hz),7.04(1H, d, J 8.5Hz), 6.86(1H, dd, J 3.5, 2.0Hz), 5.64(2H, br s) and1.44 (9H, s). 144 K 56 mp > 300° C. dec; IR ν_(max)(DR)/cm⁻¹ 2903, 2030,1606, 1464, 1033, 779 and 589; NMR δ_(H)(400MHz, DMSO) 8.30(2H, br s),8.14(1H, s), 7.92(1H, d, J 3.5Hz), 7.46(2H, d, J 8.0Hz), 7.32(2H, d, J8.0Hz), 6.92-6.84(1H, m), 5.69(2H, s) and 4.04-3.96(2H, m). 145 H 30 IRν_(max)(DR)/cm⁻¹ 3511, 3292, 3164, 2971, 1609, 1525, 1437, 1354 and1239; NMR δ_(H)(400MHz, DMSO) 8.19(2H, m), 7.90(1H, d, J 3.5Hz),7.72-7.64 (2H, m), 7.36(2H, br s), 6.53(1H, d, J 3.5Hz), 5.83(2H, s),2.80(2H, q, J 7.5Hz), and 1.27(3H, t, J 7.5Hz). 146 B 35 mp 180.0-180.5°C.; IR ν_(max)(DR)/cm⁻¹ 3325, 3206, 2976, 1734, 1604, 1341, 1024 and768; NMR δ_(H)(400MHz, DMSO) 7.92(1H, d, J 3.0Hz), 7.84(1H, s), 7.67(1H,d, J 4.0Hz), 7.62(1H, d, J 8.0Hz), 7.37(2H, br s), 7.26(1H, d, J 8.0Hz),6.87(1H, dd, J 3.5, 1.5Hz), 6.70(1H, d, J 3.5Hz), 5.80(2H, s) and 1.51(9H, s). 147 K 57 mp > 200° C. dec; IR ν_(max)(DR)/cm⁻¹ 2816, 2004,1660, 1507, 1427, 1277, 1030, 746 and 524; NMR δ_(H)(400MHz, DMSO)8.15-8.12(1H, m), 7.91(1H, d, J 3.5Hz), 7.14(1H, d, J 12.0Hz),7.06-6.94(2H, m), 6.86(1H, dd, J 3.5, 2.0Hz) and 5.57(2H, s). 148 B 43Mp 259.8-259.9° C. IR ν_(max)(DR)/cm⁻¹ 3382, 3214, 2986, 2731, 2090,1767, 1730, 1606, 1487, 1372, 1275, 1137, 1029, 873 and 771; NMRδ_(H)(400MHz, DMSO) 1.49(9H, s), 5.63(2H, s), 6.85-6.86(1H, m),7.20-7.27(2H, m), 7.40 (2H, s), 7.87(1H, d, J 3.0Hz), 8.11-8.14(1H, m).149 K 96 IR ν_(max)(Nujol)/cm⁻¹ 3375, 3061, 1653, 1509 and 1474; NMRδ_(H)(400MHz, DMSO) 11.15-10.13(1H, s), 8.43-7.36(3H, s), 8.14-8.12(1H,m), 7.89 (1H, dd, J 3.5, 1.0Hz), 6.87-6.84(1H, m), 6.59-6.51(2H, m) and5.51(2H, s). 150 C 37 IR ν_(max)(DR)/cm⁻¹ 4043, 3461, 3312, 3198, 2970,2748, 2438, 1923, 1650, 1514, 1497 and 1324; NMR δ_(H)(400MHz, DMSO)7.9(1H, d, J 3.5Hz), 7.31(2H, br s), 6.97(1H, t, J 8.0Hz), 6.53(1H, d, J3.5Hz), 6.45(1H, dd, J 1.5, 8.0Hz), 6.40(1H, d, J 7.5Hz), 6.34(1H, t, J1.7Hz), 5.48(2H, s), 5.12(2H, s), 2.80(2H, q, J 7.5Hz) and 1.27(3H, t, J7.5Hz). 151 C 48 mp 251.2-251.5° C.; IR ν_(max)(DR)/cm⁻¹ 3449, 3365,3314, 3196, 2954, 2742, 1731, 1642, 1598, 1556, 1463 and 1407; NMRδ_(H)(400MHz, DMSO) 8.76-8.72 (2H, m), 7.67-7.62(3H, m), 7.36(2H, br s),6.97(1H, t, J 8.0Hz), 6.46 (1H, dd, J 1.5, 8.0Hz), 6.43(1H, d, J 7.5Hz),6.36(1H, t, J 1.7Hz), 5.52(2H, s) and 5.13(2H, s). 152 AF 86 mp298.9-299.0° C.; IR ν_(max)(DR)/cm⁻¹ 3422, 3321, 3105, 3942, 1601, 1351,1219, 1019 and 762; NMR δ_(H)(400MHz, DMSO) 11.09(1H, br s), 8.13(1H,s), 7.91(1H, d, J 3.0Hz), 7.51(1H, d, J 8.5Hz), 7.43-7.31(3H, m),7.28(1H, s), 7.00(1H, d, J 8.0Hz), 6.89-6.83(1H, m), 6.39(1H, s) and5.73(2H, br s). 153 AF 75 mp 226.8-227.4° C.; IR ν_(max)(DR)/cm⁻¹ 3475,3320, 2739, 1645, 1506, 1223, 1008 and 778; NMR δ_(H)(400MHz, DMSO)11.14(1H, br s), 8.14-8.10(1H, m), 7.90(1H, d, J 3.5Hz), 7.50(1H, s),7.40-7.31(4H, m), 7.09(1H, dd, J 8.0, 1.5Hz), 6.85(1H, dd, J 3.5,1.5Hz), 6.43-6.38(1H, m) and 5.70(2H, s). 154 AF 77 mp 295.3-295.5° C.;IR ν_(max)(DR)/cm⁻¹ 3215, 1610, 1005, 758, 650 and 565; NMRδ_(H)(400MHz, DMSO) 11.36(1H, br s), 8.15-8.11(1H, m), 7.91(1H, d, J3.5Hz), 7.51(1H, d, J 8.0Hz), 7.46(1H, t, J 2.5Hz), 7.43(2H, br s),6.92(1H, t, J 7.5Hz), 6.86(1H, dd, J 3.5, 2.0Hz), 6.71(1H, d, J 7.0Hz),6.53-6.49(1H, m) and 5.93(2H, s). 155 B 35 mp 258.6-258.7° C.; IRν_(max)(Nujol)/cm⁻¹ 3386, 3206, 1646, 1607 and 1481; NMR δ_(H)(400MHz,DMSO) 8.33(1H, dd, J 9.0, 4.5Hz), 8.15(1H, s), 7.92(1H, d, J 3.5Hz),7.55-7.47(1H, m), 7.47-7.35(2H, s), 6.93-6.85(2H, m) and 6.03(2H, s).156 AG 99 mp 274.2-274.3° C.; IR ν_(max)(Nujol)/cm⁻¹ 3482, 3305, 3197,2963, 1606, 1499 and 1420; NMR δ_(H)(400MHz, DMSO) 8.12(1H, s), 7.87(1H,d, J 3.0Hz), 7.37 (2H, s), 6.86-6.77(3H, m), 5.55(2H, s) and 3.79(3H,s); Anal. Calcd for C₁₆H₁₂N₆O₂F₂.0.5 H₂O: C, 52.32; H, 3.57, N, 22.88.Found: C, 52.62; H, 3.31; N, 22.72. 157 B 24 mp 204.2-204.4° C.; NMRδ_(H)(400MHz, DMSO) 1.41(9H, s), 4.37,(2H, d, J 6.0Hz), 5.72(2H, s),6.83(1H, d, J 6.0Hz), 6.85-6.88(1H, d, J 7.5Hz), 7.14-7.22 (1H, m),7.30(2H, d, J 4.0Hz), 7.36(2H, s), 7.48(1H, t, J 6.0Hz), 7.91 (1H, d, J3.5Hz), 8.12-8.14(1H, m). Anal. Calcd for C₂₁H₂₃N₇O₃: C, 59.85; H, 5.50;N, 23.25. Found: C, 59.69; H, 5.54; N, 22.74. 158 AZ mp > 300° C. dec;IR ν_(max)(DR)/cm⁻¹ 3212, 1607, 1438, 1212, 1029 and 770; NMRδ_(H)(400MHz, DMSO) 15.74(1H, br s), 8.13(1H, s), 7.91(1H, d, J 3.5Hz),7.80(2H, br s), 7.54-7.30(3H, s), 6.86(1H, dd, J 4.0, 2.0Hz) and 5.85(2H, s). 159 B 16 Mp 235.9-237.8° C.; NMR δ_(H)(400MHz, DMSO)8.15-8.13(1H, m), 7.93-7.91 (1H, d, J 3.5Hz), 7.84-7.82(1H, d, J 2.5Hz),7.80-7.76(1H, dd, J 2.5, 8.5Hz), 7.43-7.37(2H, s) 7.04-7.00(1H, d, J8.5Hz), 6.89-6.86(1H, dd, J 2.0, 3.5Hz), 5.71-5.69(2H s), and3.99-3.97(3H s). 160 B 28 mp 277.4-277.9° C.; NMR δ_(H)(400MHz, DMSO)9.93(1H, s), 8.15-8.12(1H, m), 7.92(1H, d, J 3.5Hz), 7.55(1H, d, J8.0Hz), 7.38(2H, s), 7.34(1H, s), 7.27 (1H, t, J 8.0Hz), 6.96(1H, d, J7.5Hz), 6.88-6.85(1H, m), 5.63(2H, s) and 1.99(3H, s). 161 K 100 mp >250° C. dec; IR ν_(max)(DR)/cm⁻¹ 3035, 1968, 1654, 1464, 1354, 1247,1032 and 746; NMR δ_(H)(400MHz, DMSO) 4.39(2H, q, J 5.5Hz), 5.81(2H, s),6.84-6.89 (1H, m), 7.13(1H, d, J 7.5Hz), 7.31-7.46(3H, m), 7.55(1H, d, J7.5Hz), 7.90(1H, d, J 3.5Hz), 8.12-8.16(1H, m), 8.44(3H, s). Anal. Calcdfor C₁₆H₁₅N₇O.2 HCl.1.5 H₂O: C, 45.62; H, 4.79; N, 23.27. Found: C,45.63; H, 4.71; N, 23.14. 162 B 14 mp 195.1-195.2° C.; IRν_(max)(DR)/cm⁻¹ 3490, 3375, 3310, 3199, 2895, 1734, 1609, 1507, 1421,1228, 1026, 1001 and 760; NMR δ_(H)(400MHz, DMSO) 2.86 (6H, s), 5.58(2H,s), 6.48(1H, d, J 7.5Hz), 6.64(1H, dd, J 8.0, 2.0Hz), 6.72-6.75 (1H, m),6.84-6.87(1H, m), 7.12(1H, t, J 7.5Hz), 7.35(2H, s), 7.90(1H, d, J3.5Hz) and 8.10-8.14(1H, m). 163 B 20 IR ν_(max)(DR)/cm⁻¹ 3489, 3324,3199, 2560, 1605, 1235, 1121, 1048 and 762; NMR δ_(H)(400MHz, DMSO)8.12(1H, d, J 2.5Hz), 7.90(1H, d, J 3.5Hz), 7.44-7.32 (4H, m), 7.16(2H,d, J 9.0Hz), 6.86(1H, dd, J 3.5, 1.5Hz) and 5.67(2H, s). 164 B 16 mp120.1-121.0° C.; IR ν_(max)(DR)/cm⁻¹ 3318, 1772, 1709, 1607, 1462, 1395;NMR δ_(H)(400MHz, DMSO) 8.15-8.14(1H, m), 7.81(1H, d, J 3.5Hz), 7.77(1H, t, J 8.0Hz), 7.71-7.65(4H, m), 7.33(1H, d, J 8.0Hz), 7.21(2H, brs), 7.12 (1H, d, J 8.0Hz), 6.88(1H, dd, J 1.5, 3.5Hz), 5.68(2H, s),4.80(2H, s). 165 C 60 mp 259.7-259.8° C.; IR ν_(max)(DR)/cm⁻¹ 3457,3315, 3183, 2959, 2747, 1734, 1653, 1608, 1518, 1441, 1420 and 1386; NMRδ_(H)(400MHz, DMSO) 8.12(1H, d, J 1.0Hz), 7.90(1H, d, J 3.5Hz), 7.35(2H,br s), 6.93(1H, dd, J 8.0, 11.5Hz), 6.86(1H, dd, 1.5, J 3.5Hz), 6.58(1H,dd, J 2.0, J 8.5Hz) 6.47-6.39(1H, m), 5.49(2H, s) and 5.19(2H, s). 166 B10 mp 210.3-211.2° C.; NMR δ_(H)(400MHz, DMSO) 8.15-8.10(1H, m),7.89(1H, d, J 4.5Hz), 7.35(2H, br s), 7.18(1H, s), 7.08(1H, d, J 8.0Hz),6.85(1H, dd, J 3.5, 1.5Hz), 6.72(1H, d, J 8.0Hz), 5.55(1H, s), 4.49(2H,t, J 8.5Hz) and 3.13 (2H, t, J 8.5Hz). 167 B 11 IR ν_(max)(Nujol)/cm⁻¹3486, 3319, and 1606; NMR δ_(H)(400MHz, DMSO) 8.15-8.10 (1H, m),7.92-7.87(1H, d, J 3.5Hz), 7.64-7.56(1H, m), 7.54-7.47(1H, m),7.46-7.35(2H, s), 7.32-7.22(1H, t, J 9.5Hz), 6.88-6.84(1H, dd, J 2.0,3.5Hz), and 5.71-5.65(2H s); Anal. Calcd for C₁₅H₁₀N₆OFBr.0.5 H₂O: C,45.25; H, 2.78; N, 21.11. Found: C, 45.10; H, 2.48; N, 20.69. 168 B 12Mp 204.0-204.2° C.; IR ν_(max)(Nujol)/cm⁻¹ 3343 and 3208; NMRδ_(H)(400MHz, DMSO) 8.14-8.12(1H, m), 7.91-7.89(1H, dd, J 1.0, 3.5Hz),7.62-7.53(1H, m), 7.45-7.37(2H, s), 7.05-6.97(1H, m), 6.88-6.85(1H, dd,J 2.0, 3.5Hz), and 5.76-5.74(2H, s). 169 B 11 IR ν_(max)(Nujol)/cm⁻¹3490 and 3321; NMR δ_(H)(400MHz, DMSO) 8.15-8.13 (1H, m), 7.91-7.89(1H,d, J 3.5Hz), 7.78-7.72(1H, m), 7.67-7.63(1H, dd, J 2.0, 7.0Hz),7.46-7.38(2H, s), 7.15-7.08(1H, dd, J 9.0, 10.0Hz) 6.88-6.85 (1H, dd, J2.0, 3.5Hz), and 5.67-5.64(2H, s). 170 B 18 IR ν_(max)(Nujol)/cm⁻¹ 3495and 3304; NMR δ_(H)(400MHz, DMSO) 8.14-8.12 (1H, m), 7.90-7.88(1H, dd, J1.0, 3.5Hz), 7.64-7.62(1H, dd, J 1.0, 2.0Hz), 7.43-7.37(2H, s),6.87-6.84(1H, dd, J 1.5, 3.5Hz), 6.51-6.48(1H, dd, J 1.0, 3.5Hz),6.46-6.44(1H, dd, J 2.0, 3.5Hz) and 5.67-5.65(2H, s). 171 C 59 mp 219.3°C.; IR ν_(max)(Nujol)/cm⁻¹ 3508, 3421, 3307, 3190, 2949, 1609 and 1506;NMR δ_(H)(400MHz, DMSO) 8.14(1H, s), 7.91(1H, d, J 3.5Hz), 7.43(2H, s),6.92-6.85(2H, m), 6.72(1H, dd, J 8.5, 5.0Hz), 6.52(1H, dd, J 9.5,3.0Hz), 5.47(2H, s) and 5.19(2H, s). 172 B 18 IR ν_(max)(Nujol)/cm⁻¹3490, 3304, 3182, 2986, 1779, 1762, 1603, 1345 and 1231; NMRδ_(H)(400MHz, DMSO) 8.16(1H, d, J 8.5Hz), 8.15-8.13(1H, m), 7.92 (1H, d,J 3.5Hz), 7.46(1H, d, J 2.0Hz), 7.45-7.36(2H, s), 7.32(1H, dd, J 8.5,1.5Hz), 6.88-6.86(1H, m), 5.84(2H, s) and 1.47(9H, s). 173 C 78 mp239.6-239.8° C.; IR ν_(max)(Nujol)/cm⁻¹ 3323, 2936, 2733, 1772, 1734,1609, 1508 and 1282; NMR δ_(H)(400MHz, DMSO) 9.07(1H, s), 8.13-8.11(1H,m), 7.89(1H, d, J 3.5Hz), 7.34(2H, s), 6.87-6.84(1H, m), 6.59-6.50(3H,m), 5.41(2H, s) and 4.57(2H, s). 174 K 81 mp > 200° C.; dec; IRν_(max)(DR)/cm⁻¹ 3144, 2570, 2004, 1654, 1458, 1369, 1280, 1037 and 760;NMR δ_(H)(400MHz, DMSO) 7.87(1H, d, J 3.5Hz), 7.13(1H, d, J 11.5Hz),7.05-6.91(2H, m), 6.51(1H, dd, J 3.5, 1.0Hz), 5.55(2H, s) and 2.45 (3H,s). 175 C 17 mp 279.3-281.3° C.; IR ν_(max)(DR)/cm⁻¹ 3462, 3202, 2952,1653, 1510, 1462, 1416, 1342, 1293 and 1261; NMR δ_(H)(400MHz, DMSO)13.52(1H, br s), 7.97 (1H, br s), 7.31(1H, s), 7.25(2H, br s), 6.96(1H,t, J 7.5Hz), 6.46(1H, dd, J 1.0, 8.0Hz), 6.42(1H, d, J 7.0), 6.34(1H,s), 5.50(2H, s) and 5.13(2H, s). 176 K 51 IR ν_(max)(Nujol)/cm⁻¹ 3651,3488, 3317, 1637, 1507 and 1331; NMR δ_(H)(400MHz, DMSO) 11.04(1H, s),8.15-8.13(1H, m), 7.92(1H, dd, J 3.5, 1.0Hz), 7.87(1H, d, J 8.5Hz),7.41(2H, s), 6.88-6.86(1H, m), 6.85-6.81(2H, m) and 5.72(2H, s); Anal.Calcd for C₁₅H₁₁N₇O₄.1.0 H₂O: C, 48.52; H, 3.53, N, 26.24. Found: C,48.68; H, 3.20; N, 26.24. 177 AL 65 mp 245.9-247.0° C.; IRν_(max)(DR)/cm⁻¹ 3284, 3194, 1654, 1609, 1523; NMR δ_(H) (400MHz, DMSO)8.41(1H, t, J 6.0Hz), 8.14-8.13(1H, m), 7.92(1H, dd, J 1.0, 3.5Hz),7.73(1H, t, J 7.5Hz), 7.37(2H, br s), 7.21(1H, d, J 7.5Hz), 6.93 (1H, d,J 7.5Hz), 6.88-6.86(1H, m), 5.74(2H, s), 4.28(2H, d, J 6.0Hz), 1.88 (3H,s); Anal. Calcd for C₁₇H₁₆N₈O₂.0.5 H₂O.0.1 C₃H₇NO: C, 54.58; H, 4.69, N,29.80. Found: C, 54.90; H, 4.43; N, 29.46. 178 R 20 mp 216.7-218.4° C.;IR ν_(max)(DR)/cm⁻¹ 3854, 3143, 2569, 2004, 1654, 1518, 1437, 1279,1207, 1037 and 868; NMR δ_(H)(400MHz, DMSO) 1.90(3H, s), 4.48 (2H, d, J6.0Hz), 5.73(2H, s), 6.82-6.89(2H, m), 7.15-7.23(1H, m), 7.25-7.46 (4H,m), 7.91(1H, d, J 3.5Hz), 8.12-8.15(1H, m), 8.39(1H, t, J 5.5Hz). 179 B11 Mp 215.8-216.9° C.; IR ν_(max)(Nujol)/cm⁻¹ 3482 and 3305; NMRδ_(H)(400MHz, DMSO) 8.13-8.11(1H, m), 7.91-7.89(1H, d, J 3.5Hz),7.55-7.52(1H, dd, J 3.0, 5.0Hz), 7.42-7.40(1H, m), 7.39-7.34(2H, s),7.11-7.08(1H, dd, J 1.5, 5.0Hz), 6.87-6.85(1H, dd J 1.5, 3.5Hz) and5.66-5.64(2H, s); Anal. Calcd for C₁₃H₁₀N₆OS: C, 52.34; H, 3.38, N,28.16. Found: C, 52.53; H, 3.57; N, 28.22. 180 C 25 mp 278.4-279.9° C.;IR ν_(max)(DR)/cm⁻¹ 3468, 3184, 2967, 1735, 1604, 1436, 1322, 1234 and1204; NMR δ_(H)(400MHz, DMSO) 7.87(1H, d, J 3.0Hz), 7.30 (2H, br s),6.80(1H, t, J 8.0Hz), 6.58(1H, dd, J 1.0, 8.0Hz), 6.51(1H, dd, J 3.0,1.0Hz), 6.11(1H, d, J 7.0Hz), 5.54(2H, s), 4.93(2H, br s), 2.45(3H, s)and 2.1 (3H, s). 181 B 12 IR ν_(max)(Nujol)/cm⁻¹ 3501 and 3316; NMRδ_(H)(400MHz, DMSO) 8.13-8.11 (1H, m), 7.90-7.87(1H, dd, J 1.0, 3.5Hz),7.43-7.32(2H, s), 7.40-7.37(1H, d, J 5.0Hz), 6.90-6.87(1H, d, J 5.0Hz),6.86-6.84(1H, dd, J 2.0, 3.5Hz), 5.73-5.72(2H, s), and 2.37-2.35(3H, s).182 AM 30 mp 92.3-92.7° C.; IR ν_(max)(DR)/cm⁻¹ 3124, 3073, 2926, 1609,1520, 1411; NMR δ_(H)(400MHz, DMSO) 8.18-8.17(1H, m), 7.93(1H, d, J3.0Hz), 7.80(1H, t, J 7.5Hz), 7.37(1H, d, J 7.5Hz), 7.19(1H, d, J7.5Hz), 6.87(1H, dd, J 1.5, 3.5Hz), 5.94-5.75(3H, m), 5.78(2H, s),5.28-5.07(6H, m), 4.48(2H, s), 4.43-4.12 (4H, m), 4.02-3.99(2H, m);Anal. Calcd for C₂₄H₂₅N₇O₂: C, 65.00; H, 5.68, N, 22.10. Found: C,65.23; H, 5.80; N, 21.60. 183 B 27 mp 152.0-153.5° C.; IRν_(max)(DR)/cm⁻¹ 3515, 3300, 3183, 2934, 2822, 1631, 1450, 1434; NMRδ_(H)(400MHz, DMSO) 7.89(1H, d, J 3.0Hz), 7.79(1H, t, J 7.5Hz), 7.33(2H,br s), 7.34(1H, d, J 7.5Hz), 7.02(1H, d, J 7.5Hz), 6.53-6.51 (1H, m),5.74(2H, s), 4.43(2H, s), 2.46(3H, s), 3.33(3H, s); Anal. Calcd forC₁₇H₁₇N₇O₂: C, 58.11; H, 4.88, N, 27.89. Found: C, 57.75; H, 4.85; N,27.59. 184 C 76 mp 219.7-220.4° C.; IR ν_(max)(DR)/cm⁻¹ 3450, 3312,2920, 2728, 1737, 1638, 1438, 1354, 1326, 1291 and 1234; NMRδ_(H)(400MHz, DMSO) 7.85(1H, d, J 3.0Hz), 7.30(2H, br s), 7.01(2H, d, J8.5Hz), 6.52-6.47(3H, m), 5.41(2H, s), 5.12(2H, s) and 2.44(3H, s). 185B 15 mp 155.6-157.1° C.; IR ν_(max)(DR)/cm⁻¹ 3332, 3197, 2857, 1655,1605, 1525, 1420; NMR δ_(H)(400MHz, DMSO) 8.14-8.13(1H, m), 7.92(1H, d,J 3.5Hz), 7.79(1H, t, J 7.5Hz), 7.37(1H, d, J 7.5Hz), 7.36(2H, br s),7.05(1H, d, J 7.5Hz), 6.88-6.86(1H, m), 5.98-5.86(1H, m), 5.76(2H, s),5.29-5.24(1H, m), 5.17-5.13(1H, m), 4.48(2H, s), 4.06-4.00(2H, m); Anal.Calcd for C₁₈H₁₇N₇O₂: C, 59.50; H, 4.72, N, 26.97. Found: C, 59.39; H,4.70; N, 26.99. 186 B 23 mp 149.0-149.3° C.; IR ν_(max)(DR)/cm⁻¹ 3514,3295, 3168, 2861, 1634, 1502, 1435; NMR δ_(H)(400MHz, DMSO) 7.88(1H, d,J 3.5Hz), 7.79(1H, t, J 7.5Hz), 7.37(1H, d, J 7.5Hz), 7.33(2H, br s),7.04(1H, d, J 7.5Hz), 6.52-6.51(1H, m), 5.96-5.86(1H, m), 5.74(2H, s),5.30-5.24(1H, m), 5.17-5.13(1H, m), 4.49(2H, s), 4.06-4.00(2H, m),2.46(3H, s); Anal. Calcd for C₁₉H₁₉N₇O₂.0.2 H₂O: C, 59.90; H, 5.13, N,25.73. Found: C, 59.71; H, 5.02; N, 25.64. 187 B 20 mp 191.7-191.9° C.;IR ν_(max)(Nujol)/cm⁻¹ 3501, 3307, 3189, 2974, 1611, 1527 and 1338; NMRδ_(H)(400MHz, DMSO) 8.12-8.15(1H, m), 7.91(1H, d, J 3.5Hz), 7.76(1H, d,J 8.5Hz), 7.67(1H, d, J 2.0Hz), 7.44-7.36(2H, s), 7.16(1H, dd, J 8.5,2.0Hz), 6.87-6.85(1H, m), 5.78(2H, s), 3.22(1H, quin, J 6.5Hz) and1.22(6H, d J 6.5Hz). 188 B 32 mp 228.9-229.9° C.; IR ν_(max)(DR)/cm⁻¹3461, 3317, 3195, 1606, 1504, 1320, 1026 and 818; NMR δ_(H)(400MHz,DMSO) 8.16-8.14(1H, m), 7.98(1H, d, J 8.0Hz), 7.94(1H, d, J 3.5, 1.0Hz),7.91(1H, d, J 8.0Hz), 7.78-7.73(1H, m), 7.64-7.58 (1H, m), 7.36(1H, d, J8.5Hz), 7.36(2H, br s), 6.88(1H, dd, J 3.5, 1.5Hz) and 5.98(2H, s). 189K 23 NMR δ_(H)(400MHz, DMSO) 8.14-8.12(1H, m), 7.92-7.89(1H, dd, J 1.0,3.5Hz), 7.35-7.31(2H, d, J 8.5Hz), 7.28-7.16(2H, s), 6.88-6.85(1H, dd, J1.5, 3.5Hz), 5.66-5.64(2H, s), and 2.82-2.80(3H, s); M/Z 322(M+H)⁺. 190B 37 mp 290.2-290.3° C.; IR ν_(max)(DR)/cm⁻¹ 3491, 3338, 3205, 3128,2936, 1710, 1616, 1490, 1458; NMR δ_(H)(400MHz, DMSO) 8.13-8.12(1H, m),7.93(1H, t, J 7.5Hz), 7.90(1H, dd, J 1.0, 3.5Hz), 7.84(1H, d, J 7.5Hz),7.56(1H, d, J 7.5Hz), 7.34(2H, br s), 6.86(1H, dd, J 2.0, 3.5Hz),6.69(1H, q, J 7.5Hz), 2.48 (3H, s), 1.98(3H, d, J 7.5Hz); Anal. Calcdfor C₁₇H₁₅N₇O₂: C, 58.45; H, 4.33, N, 28.05. Found: C, 58.26; H, 4.42;N, 27.67. 191 C 16 mp 186.1-189.1° C.; IR ν_(max)(DR)/cm⁻¹ 3458, 1598,1509, 1460, 1329, 1267 and 1220; NMR δ_(H)(400MHz, DMSO) 11.73(1H, s),7.59(1H, s), 7.17(1H, s), 6.97 (1H, t, J 7.8Hz), 6.95-6.83(2H, br s),6.45(1H, dd, J 1.5, J 8.0Hz), 6.40(1H, d, J 8.0Hz), 6.38-6.31(1H, m),5.47(2H, s) and 5.13(2H, s). 192 Q 2 NMR δ_(H)(400MHz, CD₃OD) 8.84(1H,d, J 4.5Hz), 8.77(1H, d, J 8.0Hz), 8.33 (1H, t, J 1.7Hz), 8.2(1H, dd, J2.0, 8.0Hz), 8.06(1H, td, J 7.8, 2.0Hz), 7.81 (1H, d, J 7.5Hz),7.65-7.58(2H, m) and 5.88(2H, s); M/Z 349(M+H)⁺; Retention time 1.77min. 193 B 6 mp 253.6-254.0° C.; IR ν_(max)(DR)/cm⁻¹ 3320, 1611, 1414,1315, 1255, 1026 and 767; NMR δ_(H)(400MHz, DMSO) 2.01(3H, s), 5.59(2H,s), 6.84-6.88(1H, m), 7.22(2H, d, J 8.5Hz), 7.36(2H, s), 7.54(2H, d, J8.5Hz) 7.90(1H, d, J 3.5Hz), 8.11-8.14(1H, m), 9.97(1H, s). 194 B 36 mp136.5-137.6° C.; IR ν_(max)(Nujol)/cm⁻¹ 3489, 3311, 3195, 2954, 1774 and1613; NMR δ_(H)(400MHz, DMSO) 8.24(1H, s), 8.04(1H, d, J 2.0Hz), 8.00(1H, d, J 3.5Hz), 7.96(1H, dd, J 8.5, 2.0Hz), 7.52-7.44(2H, s), 7.40(1H,d, J 8.5Hz), 6.99-6.95(1H, m), 5.83(2H, s), 5.54(2H, s), 3.66(2H, t, J8.0Hz), 0.93(2H, t, J 8.0Hz) and 0.00(9H, s); Anal. Calcd forC₂₁H₂₅N₇O₅Si.0.1 H₂O: C, 51.97; H, 5.23, N, 20.20. Found: C, 51.97; H,5.19; N, 19.86. 195 B 12 IR ν_(max)(Nujol)/cm⁻¹ 3652, 3506, 3307, 3196,2990, 2878, 1633, 1521 and 1344; NMR δ_(H)(400MHz, DMSO) 8.14(1H, s),7.94-7.88(2H, m), 7.46(1H, s), 7.40 (2H, s), 7.23(1H, dd, J 8.5, 2.0Hz),6.88-6.85(1H, m), 5.78(2H, s), 2.80(2H, q, 7.5Hz) and 1.17(3H, t, J7.5Hz); Anal. Calcd for C₁₇H₁₅N₇O₃.0.25 H₂O: C, 55.21; H, 4.22, N,26.51. Found: C, 55.47; H, 4.12; N, 26.25. 196 B 23 mp 178.4-179.0° C.;IR ν_(max)(Nujol)/cm⁻¹ 3469 and 3311; NMR δ_(H)(400MHz, DMSO)8.13-8.11(1H, m), 7.90-7.88(1H, dd, J 1.0, 3.5Hz), 7.37-7.32(2H, s),7.32-7.29(1H, dd, J 1.5, 5.5Hz), 6.92-6.89(1H, dd, J 3.5, 5.5Hz),6.87-6.84 (2H, m), 4.70-4.64(2H, t, J 7.0Hz), and 3.53-3.48(2H, t, J7.0Hz); Anal. Calcd for C₁₄H₁₂N₆OS: C, 53.84; H, 3.87; N, 26.89. Found:C, 53.98; H, 3.87; N, 26.50. 197 B 22 mp 188.3-188.5° C.; IRν_(max)(DR)/cm⁻¹ 3324, 3189, 2964, 1649, 1513; NMR δ_(H) (400MHz, DMSO)8.14-8.13(1H, m), 7.93(1H, d, J 3.5Hz), 7.67(1H, t, J 7.5Hz), 7.34(2H,br s), 7.20(1H, d, J 7.5Hz), 6.89(1H, d, J 7.5Hz), 6.87-6.86 (1H, m),5.75(2H, s), 2.93(1H, sept, J 7.0Hz), 1.12(6H, d, J 7.0Hz); Anal. Calcdfor C₁₇H₁₇N₇O: C, 60.88; H, 5.11, N, 29.22. Found: C, 61.03; H, 5.13; N,28.95. 198 B 27 IR ν_(max)(DR)/cm⁻¹ 3466, 3312, 3187, 2958, 2850, 1639,1511, 1221, 1047, 756 and 599; NMR δ_(H)(400MHz, DMSO) 8.13(1H, s),8.09(1H, s), 7.91(1H, d, J 3.0Hz), 7.72(1H, d, J 8.5Hz), 7.68(1H, s),7.42(1H, d, J 8.5Hz), 7.37(2H, br s), 6.88-6.83(1H, m), 5.82(1H, d, J9.5Hz), 5.77(2H, s), 3.90-3.80(1H, m), 3.77-3.64(1H, m), 2.45-2.30(1H,m), 2.10-1.88(2H, m), 1.80-1.63(1H, m), 1.62-1.49(2H, m). 199 B 7 mp226.5-227.9° C.; IR ν_(max)(DR)/cm⁻¹ 3466, 3316, 3182, 2962, 1645, 1606,1546, 1514, 1473; NMR δ_(H)(400MHz, DMSO) 8.14-8.13(1H, m), 7.92(1H, d,J 3.0Hz), 7.33(2H, br s), 7.07-7.06(1H, m), 6.88-6.86(2H, m), 5.71(2H,s), 2.88(1H, sept, J 7.0Hz), 2.82(1H, sept, J 7.0Hz), 1.14(6H, d, J7.0Hz), 1.09 (6H, d, J 7.0Hz). 200 K 99 mp > 300° C. dec; IRν_(max)(DR)/cm⁻¹ 3100, 1662, 1465, 1281, 1032, 782 and 592; NMRδ_(H)(400MHz, DMSO) 8.16-8.13(1H, m), 8.07(1H, s), 7.92(1H, d, J 3.5Hz),7.68(1H, s), 7.54(1H, d, J 8.5Hz), 7.35(1H, dd, 8.5, 1.5Hz), 6.87(1H,dd, J 3.5, 2.0Hz) and 5.76(1H, s) 201 K 99 IR ν_(max)(Nujol)/cm⁻¹ 2999,1656, 1530 and 1461; NMR δ_(H)(400MHz, DMSO) 11.10(1H, s), 8.14(1H, d, J1.0Hz), 7.92(1H, d, J 3.5Hz), 7.72(1H, d, J 2.5Hz), 7.61(1H, dd, J 8.5,2.5Hz), 7.0(1H, d, J 8.5Hz), 6.86-6.88(1H, m), 5.67 (2H, s) and5.11-5.16(3H, s). 202 B 32 mp 210.5-211.6° C.; IR ν_(max)(FILM)/cm⁻¹3352, 3204, 3001, 1659, 1569, 1510, 1440; NMR δ_(H)(400MHz, DMSO)8.14(1H, m), 7.93(1H, d, J 3.5Hz), 7.76 (1H, t, J 7.5Hz), 7.43(1H, d, J7.5Hz), 7.36(2H, br s), 7.03(1H, d, J 7.5Hz), 6.87(1H, dd, J 2.0,3.5Hz), 6.75(1H, dd, J 10.5, 17.5Hz), 6.09(1H, dd, J 2.0, 17.5Hz),5.78(2H, s), 5.43(1H, dd, J 1.5, 10.5Hz); Anal. Calcd for C₁₆H₁₃N₇O: C,60.18; H, 4.10, N, 30.69. Found: C, 60.14; H, 4.20; N, 30.39. 203 AS 12IR ν_(max)(Nujol)/cm⁻¹ 3514, 3298 and 1761; NMR δ_(H)(400MHz, DMSO)8.16-8.15 (1H, m), 7.89-7.86(1H, dd, J 1.0, 3.5Hz), 7.80-7.40(2H, s),6.89-6.86 (1H, dd, J 1.5, 3.5Hz), and 1.66-1.64(9H, s). 204 B 16 mp143.6-144.5° C.; IR ν_(max)(DR)/cm⁻¹ 3644, 3315, 3195, 2978, 1743, 1608,1163, 1086 and 746; NMR δ_(H)(400MHz, DMSO) 8.14-8.10(1H, m), 8.05(1H,d, J 8.0Hz), 7.88(1H, d, J 3.5Hz), 7.81(1H, s), 7.66(1H, d, J 7.5Hz),7.42 (2H, br s), 7.34(1H, t, J 8.0Hz), 7.23(1H, t, J 8.0Hz), 6.85(1H,dd, J 3.5, 2.0Hz), 5.78(2H, s) and 1.63(9H, s) 205 B 19 IRν_(max)(DR)/cm⁻¹ 3431, 3325, 3217, 1646, 1504, 1431; NMR δ_(H)(400MHz,DMSO) 9.87-9.86(1H, m), 8.14(1H, m), 8.05(1H, t, J 8.0Hz), 7.94-7.92(1H, m), 7.88(1H, d, J 8.0Hz), 7.52(1H, d, J 8.0Hz), 7.38(2H, br s),6.88-6.87 (1H, m), 5.91(2H, s); Anal. Calcd for C₁₅H₁₁N₇O₂.0.3 H₂O: C,55.15; H, 3.58, N, 30.01. Found: C, 55.33; H, 3.35; N, 29.64. 206 B 30IR ν_(max)(film)/cm⁻¹ 3327, 3209, 2987, 1730, 1664, 1390, 1168, 959, 745and 664; NMR δ_(H)(400MHz, DMSO) 8.16(1H, s), 8.09(1H, d, J 8.0Hz),7.97-7.92 (2H, m), 7.47(1H, d, J 7.5Hz), 7.44-7.35(2H, br s), 7.31(1H,t, J 7.5Hz), 7.20 (1H, t, J 7.0Hz), 6.89(1H, dd, J 3.5, 1.5Hz),6.03-5.96(3H, m) and 1.64(9H, s) 207 AF 71 mp 289.1-289.3° C.; IRν_(max)(DR)/cm⁻¹ 3442, 3317, 3189, 1649, 1607, 1519, 1332, 1118, 1023and 763; NMR δ_(H)(400MHz, DMSO) 11.21(1H, br s), 8.13 (1H, s), 7.91(1H,d, J 3.5Hz), 7.46(1H, d, 8.0Hz), 7.38(2H, br s), 7.33(1H, d, J 8.0Hz),7.06(1H, t, J 8.0Hz), 6.96(1H, t, J 7.0Hz), 6.86(1H, dd, J 3.5, 1.5Hz),6.31(1H, s) and 5.79(2H, s) 208 B 4 NMR δ_(H)(400MHz, DMSO)8.13-8.12(1H, m), 7.91-7.88(1H, dd, J 1.5, 3.5Hz), 7.46-7.36(2H, s),6.98-6.96(1H, d, J 3.5Hz), 6.87-6.84(1H, dd, J 1.5, 3.5Hz),6.72-6.69(1H, d, J 3.5Hz), 5.76-5.74(2H, s), 2.52-2.48(2H, h, J 2.0,3.5Hz) and 1.20-1.14(3H, t, J 7.5Hz); M/Z 327(M+H)⁺. 209 B 17 mp > 250°C.; dec; IR ν_(max)(DR)/cm⁻¹ 3489, 3316, 2919, 1610, 1326, 1037, 862,760 and 593; NMR δ_(H)(400MHz, DMSO) 8.13-8.11(1H, m), 7.90(1H, d, J2.5Hz), 7.38(2H, br s), 6.92(1H, d, J 2.0Hz), 6.88(1H, d, J 8.0Hz),6.86(1H, dd, J 3.5, 2.0Hz), 6.79(1H, dd, J 8.0, 1.5Hz), 6.00(2H, s) and5.56(2H, s). 210 C 36 IR ν_(max)(DR)/cm⁻¹ 3427, 3318, 3201, 2966, 1605,1503, 1415, 1281, 1027 and 762; NMR δ_(H)(400MHz, DMSO) 1.08(3H, t, J7.0Hz), 2.39(2H, q, J 7.0Hz), 4.91(2H, s), 5.44(2H, s), 6.54(1H, d, J8.0Hz), 6.80-9.62(2H, m), 6.97(1H, s), 7.34(2H, s), 7.89(1H, s),8.12(1H, s). Anal. Calcd for C₁₇H₁₇N₇O.0.6 H₂O: C, 58.98; H, 5.30; N,28.32. Found: C, 59.37; H, 5.02; N, 28.05. 211 AT 13 mp 257.1-257.3° C.;IR ν_(max)(DR)/cm⁻¹ 3491, 3343, 3205, 3131, 2971, 1973, 1691, 1626,1499, 1437, 1239, 1030 and 764; NMR δ_(H)(400MHz, DMSO) 6.26 (2H, s),6.86-6.91(1H, m), 7.33(2H, s), 7.63(2H, t, J 7.5Hz), 7.77(1H, t, J7.5Hz), 7.94(1H, d, J 3.0Hz), 8.11-8.16(3H, m). 212 R 58 IRν_(max)(DR)/cm⁻¹ 3321, 1608, 1438, 1304, 1025 and 757; NMR δ_(H)(400MHz,DMSO) 5.67(2H, s), 6.86-6.88(1H, m), 7.05(1H, d, J 7.5Hz), 7.20(1H, dd,J 5.0, 3.5Hz), 7.35(1H, t, J 8.0Hz), 7.39(2H, s), 7.55-7.58(1H, m),7.72(1H, d, J 7.5Hz), 7.85(1H, dd, J 5.0, 1.0Hz), 7.92(1H, d, J 3.5Hz),7.98(1H, dd, J 3.5, 1.0Hz), 8.12-8.15(1H, m), 10.24(1H, s). 213 AU 29 IRν_(max)(DR)/cm⁻¹ 3285, 1975, 1625, 1461; NMR δ_(H)(400MHz, DMSO) 8.14(1H, m), 7.92(1H, d, J 3.0Hz), 7.80(1H, t, J 7.5Hz), 7.44(1H, d, J7.5Hz), 6.98(1H, d, J 7.5Hz), 6.87(1H, dd, J 1.5, 3.5Hz), 5.75(2H, s),4.52(2H, s). 214 R 43 IR ν_(max)(DR)/cm⁻¹ 3321, 2956, 1610, 1234, 1027and 757; NMR δ_(H)(400MHz, DMSO) 0.99(9H, s), 2.14(2H, s), 5.63(2H, s),6.85-6.89(1H, m), 6.94(1H, d, J 8.0Hz), 7.27(1H, t, J 7.5Hz),7.33-7.45(3H, m), 7.59(1H, d, J 9.0Hz), 7.92 (1H, d, J 3.5Hz),8.12-8.15(1H, m). 215 R 52 IR ν_(max)(DR)/cm⁻¹ 3510, 3278, 1631, 1425,1293, 1217, 1024 and 757; NMR δ_(H) (400MHz, DMSO) 0.71-0.79(4H, m),1.72(1H, tt, J 5.5, 7.0Hz), 5.63(2H, s), 6.85-6.89(1H, m), 6.96(1H, d, J8.0Hz), 7.27(1H, t, J 7.5Hz), 7.32-7.45 (3H, m), 7.55(1H, d, J 8.0Hz),7.92(1H, dd, J 3.5, 1.0Hz), 8.12-8.15(1H, m), 10.19(1H, s). Anal. Calcdfor C₁₉H₁₇N₇O₂.0.15 H₂O: C, 60.36; H, 4.61; N, 25.93. Found: C, 60.89;H, 4.62; N, 25.54. 216 B 15 mp 178.3-178.5° C.; IR ν_(max)(DR)/cm⁻¹3472, 3324, 3194, 2964, 1641, 1598, 1510; NMR δ_(H)(400MHz, DMSO)8.14(1H, m), 7.92(1H, dd, J 1.0, 3.5Hz), 7.66(1H, t, J 8.0Hz), 7.35(2H,br s), 7.17(1H, d, J 8.0Hz), 6.90(1H, d, J 8.0Hz), 6.87(1H, dd, J 2.0,3.5Hz), 5.73(2H, s), 2.63(2H, t, J 7.5Hz), 1.59(2H, sext, J 7.5Hz),0.83(3H, t, J 7.5Hz); Anal. Calcd for C₁₇H₁₇N₇O.0.1 C₄H₈O₂: C, 60.72; H,5.21, N, 28.49. Found: C, 60.85; H, 5.22; N, 28.29. 217 B 16 mp146.7-149.3° C.; IR ν_(max)(DR)/cm⁻¹ 3518, 3323, 2955, 1605, 1511; NMRδ_(H) (400MHz, DMSO) 8.14-8.13(1H, m), 7.92(1H, d, J 3.5Hz), 7.79(1H, t,J 7.5Hz), 7.35(2H, br s), 7.35(1H, d, J 7.5Hz), 7.05(1H, d, J 7.5Hz),6.87(1H, dd, J 1.5, 3.5Hz), 5.75(2H, s), 4.46(2H, s), 3.22(2H, d, J6.5Hz), 1.77-1.87(1H, m), 0.85(6H, d, J 6.5Hz); Anal. Calcd forC₁₉H₂₁N₇O₂.0.5 H₂O: C, 58.75; H, 5.71, N, 25.24. Found: C, 58.87; H,5.49; N, 24.92. 218 B 14 mp 196.0-196.1° C.; IR ν_(max)(DR)/cm⁻¹ 3481,3325, 3203, 1646, 1607, 1518, 1488; NMR δ_(H)(400MHz, DMSO) 8.14(1H, m),7.92(1H, d, J 3.5Hz), 7.80 (1H, t, J 7.5Hz), 7.50(1H, d, J 7.5Hz),7.38(2H, br s), 7.04(1H, d, J 7.5Hz), 6.87(1H, dd, J 1.5, 3.5Hz),5.77(2H, s), 4.64(2H, s). 219 C 37 IR ν_(max)(DR)/cm⁻¹ 3480, 3379, 3199,2958, 2761, 2104, 1879, 1776, 1659, 1516, 1439, 1334, 1024, 762 and 575;NMR δ_(H)(400MHz, DMSO) 1.10(6H, d, J 7.0Hz), 2.92(1H, sept, J 6.5Hz),4.93(2H, s), 5.44(2H, s), 6.54(1H, d, J 8.0Hz), 6.80-6.88(2H, m),7.09(1H, d, J 2.0Hz), 7.34(2H, s), 7.88(1H, d, J 3.5Hz), 8.10-8.13(1H,m). Anal. Calcd for C₁₈H₁₉N₇O.0.3 H₂O: C, 60.93; H, 5.57; N, 27.63.Found: C, 60.77; H, 5.50; N, 27.42. 220 AV 26 mp 223.3-223.4° C.; NMRδ_(H)(400MHz, DMSO) 8.14(1H, m), 7.92(1H, dd, J 1.0, 3.5Hz), 7.82(1H, t,J 7.5Hz), 7.37(1H, d, J 7.5Hz), 7.36(2H, br s), 7.07 (1H, d, J 7.5Hz),6.87(1H, dd, J 1.5, 3.5Hz), 5.78(2H, s), 4.18(2H, s). 221 AW 7 NMRδ_(H)(400MHz, DMSO) 9.48-9.45(1H, s), 8.12-8.10(1H, m), 7.90-7.88 (1H,dd, J 1.0, 3.5Hz), 7.36-7.30(2H, s), 7.17-7.12(2H, dd, J 2.0, 8.5Hz),6.86-6.84(1H, dd, J 2.0, 3.5Hz), 6.74-6.70(2H, dd, J 2.0, 8.5Hz) and5.53-5.51 (2H, s); M/Z 309(M+H)⁺. 222 B 18 IR ν_(max)(DR)/cm⁻¹ 3483,3319, 3200, 2961, 1953, 1709, 1612, 1439, 1343, 1220, 995 and 761; NMRδ_(H)(400MHz, DMSO) 6.37(2H, s), 6.86-6.91(1H, m), 7.35(2H, s), 7.94(1H,d, J 3.0Hz), 8.15(1H, s), 8.37(2H, d, J 8.5Hz), 8.43 (2H, d, J 8.5Hz).Anal. Calcd for C₁₆H₁₁N₇O₄.0.2 H₂O: C, 52.09; H, 3.11; N, 26.58. Found:C, 51.94; H, 3.05; N, 26.27. 223 B 41 IR ν_(max)(DR)/cm⁻¹ 4013, 3601,3456, 3209, 2959, 2237, 1938, 1708, 1625, 1505, 1171, 1002, 827 and 733;NMR δ_(H)(400MHz, DMSO) 6.33(2H, s), 6.84-6.91 (1H, m), 7.34(2H, s),7.94(1H, d, J 3.5Hz), 8.09-8.18(3H, m), 8.28(2H, d, J 8.0Hz). Anal.Calcd for C₁₇H₁₁N₇O₂.0.7 H₂O: C, 57.05; H, 3.49; N, 27.39. Found: C,56.97; H, 3.12; N, 27.37. 224 AX 54 IR ν_(max)(DR)/cm⁻¹ 3423, 3321,3212, 1641, 1511, 1420, 1316, 1136 and 780; NMR δ_(H)(400MHz, DMSO)0.87(3H, t, J 7.5Hz), 1.54-1.66(2H, m), 2.96-3.04 (2H, m), 5.65(2H, s),6.85-6.88(1H, m), 7.00-7.03(2H, m), 7.10-7.16 (1H, m), 7.30(1H, t, J7.5Hz), 7.36(2H, s), 7.91(1H, dd, J 3.5, 1.0Hz), 8.12-8.15 (1H, m),9.79(1H, s). Anal. Calcd for C₁₈H₁₉N₇O₃S: C, 52.29; H, 4.63; N, 23.70.Found: C, 52.22; H, 4.70; N, 23.36. 225 AX 47 IR ν_(max)(DR)/cm⁻¹ 3477,3319, 3114, 1609, 1479, 1414, 1349, 1162, 956 and 763; NMR δ_(H)(400MHz,DMSO) 5.63(2H, s), 5.85-6.89(1H, m), 6.92(1H, t, J 1.5Hz), 7.02-7.11(3H,m), 7.26-7.33(2H, m), 7.37(2H, s), 7.93(1H, dd, J 3.5, 1.0Hz),8.12-8.15(1H, m), 10.62(1H, s). 226 AY 58 mp 221.4-221.5° C.; IRν_(max)(DR)/cm⁻¹ 3569, 3134, 2701, 2421, 1656, 1460; NMR δ_(H)(400MHz,DMSO) 8.14(1H, m), 7.92(1H, dd, J 1.0, 3.5Hz), 7.88 (1H, t, J 7.5Hz),7.48(1H, d, J 7.5Hz), 7.16(1H, d, J 7.5Hz), 6.88-6.87(1H, m), 5.80(2H,s), 4.27-4.24(2H, m), 2.60-2.56(3H, m). 227 B 24 IR ν_(max)(DR)/cm⁻¹4011, 3491, 3377, 3210, 3125, 2975, 2663, 2106, 1924, 1740, 1618, 1438,1201, 1004, 796 and 752: NMR δ_(H)(400MHz, DMSO) 1.14(6H, t, J 6.5Hz),3.46(4H, q, J 6.5Hz), 6.00(2H, s), 6.76(2H, d, J 9.0Hz), 6.87(1H, s),7.26(2H, s), 7.85-7.97(3H, m), 8.13(1H, s), Anal. Calcd forC₂₀H₂₁N₇O₂.0.6 H₂O: C, 59.72; H, 5.56; N, 24.38, Found: C, 60.00; H,5.40; N, 24.03. 228 B 26 mp 164.3-169.3° C.; IR ν_(max)(DR)/cm⁻¹ 3376,3199, 2964, 1659, 1613, 1516, 1441; NMR δ_(H)(400MHz, DMSO) 8.53(1H, d,J 2.0Hz), 8.12-8.11(1H, m), 7.89(1H, d, J 3.5Hz), 7.62(1H, dd, J 2.5,8.0Hz), 7.35(2H, br s), 7.26(1H, d, J 7.5Hz), 6.85(1H, dd, J 1.5,3.5Hz), 5.67(2H, s), 2.99(1H, sept, J 7.0Hz), 1.20 (6H, d, J 7.0Hz);Anal. Calcd for C₁₇H₁₇N₇O.0.5 H₂O: C, 59.29; H, 5.27, N, 28.47. Found:C, 59.28; H, 5.16; N, 28.23. 229 B 40 mp 258.2-258.4° C.; IRν_(max)(DR)/cm⁻¹ 3367, 3200, 2932, 1671, 1243, 1178, 1033, 797 and 610;NMR δ_(H)(400MHz, DMSO) 8.12-8.07(3H, m), 7.91(1H, d, J 3.5Hz),7.15-7.09(4H, m), 6.85(1H, dd, J 3.5, 1.5Hz), 6.10(2H, s) and 3.89(3H,s). 230 B 25 IR ν_(max)(DR)/cm⁻¹ 3436, 3320, 3208, 2977, 1609, 1370,1323, 1155, 1025, 840 and 768; NMR δ_(H)(400MHz, DMSO) 8.12-8.10(1H, m),7.89(1H, d, J 3.5Hz), 7.78(1H, d, J 4.0Hz), 7.73(1H, d, J 2.5Hz),7.33(2H, br s), 6.88-6.84 (2H, m), 6.76(1H, d, J 4.0Hz), 6.07(2H, s) and1.50(9H, s). 231 AF 76 mp 321.8-322.2° C.; IR ν_(max)(DR)/cm⁻¹ 3993,3233, 1645, 1515, 1437, 1336, 1102, 854 and 759; NMR δ_(H)(400MHz, DMSO)11.56(1H, br s), 8.13-8.11 (1H, m), 7.91(1H, d, J 3.5Hz), 7.58(1H, d, J2.0Hz), 7.55(1H, t, J 3.5Hz), 7.42(2H, br s), 6.86(1H, dd, J 3.5,2.0Hz), 6.73(1H, d, J 2.0Hz), 6.52(1H, dd, J 3.0, 2.0Hz) and 5.94(2H,s). 232 AX 20 IR ν_(max)(DR)/cm⁻¹ 3216, 1713, 1610, 1505, 1421, 1185,1124, 1026, 886 and 763; NMR δ_(H)(400MHz, DMSO) 2.13(3H, s), 2.35(3H,s), 5.62(2H, s), 6.85-6.88 (1H, m), 6.90-6.94(1H, m), 6.98-7.03(1H, m),7.11(1H, d, J 8.0Hz), 7.30 (1H, t, J 7.5Hz), 7.31(2H, s), 7.91(1H, d, J3.5Hz), 8.11-8.14(1H, m), 10.46 (1H, s). 233 AV 40 mp 219.7-222.3° C.;IR ν_(max)(DR)/cm⁻¹ 3326, 3191, 2821, 2772, 1595, 1504, 1432; NMRδ_(H)(400MHz, DMSO) 8.13-8.12(1H, m), 7.91(1H, dd, J 1.0, 3.5Hz),7.74(1H, t, J 7.5Hz), 7.35(1H, d, J 7.5Hz), 7.31(2H, br s), 6.98(1H, d,J 7.5Hz), 6.86(1H, dd, J 2.0, 3.5Hz), 5.74(2H, s), 3.46(2H, s), 2.15(6H,s); Anal. Calcd for C₁₇H₁₈N₈O: C, 58.28; H, 5.18, N, 31.97. Found: C,57.94; H, 5.17; N, 31.70. 234 AV 55 mp 168.3-168.5° C.; IRν_(max)(DR)/cm⁻¹ 3416, 3322, 3180, 2911, 1646, 1612, 1509, 1436; NMRδ_(H)(400MHz, DMSO) 8.13-8.12(1H, m), 7.91(1H, dd, J 1.0, 3.5Hz),7.74(1H, t, J 7.5Hz), 7.32(1H, d, J 7.5Hz), 7.31(2H, br s), 7.02(1H, d,J 7.5Hz), 6.87-6.86(1H, m), 5.75(2H, s), 3.69(2H, s), 1.92(3H, s); Anal.Calcd for C₁₆H₁₅N₇OS.0.2 H₂O: C, 53.83; H, 4.35, N, 27.46. Found: C,53.74; H, 4.29; N, 27.13. 235 B 3 mp 231.6-231.7° C.; IRν_(max)(DR)/cm⁻¹ 3642, 3320, 3198, 1727, 1533, 1437, 1223, 1029, 842 and639; NMR δ_(H)(400MHz, DMSO) 8.18(1H, d, J 7.5Hz), 8.13(1H, s),8.00-7.93(2H, m), 7.91(1H, d, J 3.5Hz), 7.89-7.82(1H, m), 7.34(2H, brs), 6.87(1H, dd, J 3.5, 1.5Hz) and 6.01(2H, s). 236 AX 32 NMRδ_(H)(400MHz, DMSO) 2.19(3H, s), 3.50(3H, s), 5.58(2H, s), 6.84-6.97(3H, m), 7.08(1H, d, J 8.0Hz), 7.20(1H, t, J 7.5Hz), 7.35(2H, s),7.58(1H, s), 7.91(1H, d, J 3.0Hz), 8.13(1H, s) and 10.14(1H, s);retention time 0.97 min. 237 AV 40 mp 259.3-259.4° C.; IRν_(max)(DR)/cm⁻¹ 3323, 3202, 1607, 1511; NMR δ_(H)(400MHz, DMSO)8.12-8.11(2H, m), 7.91(2H, dd, J 1.0, 3.5Hz), 7.70-7.66(2H, m), 7.30(4H,br s), 7.10(4H, d, J 8.0Hz), 6.85(2H, dd, J 1.5, 3.5Hz), 5.73(4H, s),4.23(4H, s), 2.78(3H, s). 238 AV 17 mp 238.2-238.6° C.; IRν_(max)(DR)/cm⁻¹ 3189, 2908, 1653, 1592, 1470; NMR δ_(H) (400MHz, DMSO)8.13-8.12(1H, m), 7.91(1H, d, J 3.0Hz), 7.85(1H, t, J 7.5Hz), 7.43(1H,d, J 7.5Hz), 7.30(2H, br s), 7.23(1H, d, J 7.5Hz), 6.87-6.85 (1H, m),5.81(2H, s), 4.56(2H, s), 2.87(3H, s). 239 AV 71 mp 205.8-206.0° C.; IRν_(max)(Nujol)/cm⁻¹ 3502, 3304, 3185, 2923, 1628, 1510; NMRδ_(H)(400MHz, DMSO) 8.13-8.12(1H, m), 7.92(1H, d, J 3.0Hz), 7.83 (1H, t,J 8.0Hz), 7.33(1H, d, J 8.0Hz), 7.30(2H, br s), 7.17(1H, d, J 8.0Hz),6.87-6.86(1H, m), 5.79(2H, s), 4.31(2H, s), 2.84(3H, s), 2.67(3H, s);Anal. Calcd for C₁₇H₁₈N₈O₃S: C, 49.27; H, 4.38, N, 27.02. Found: C,49.14; H, 4.49; N, 26.74. 240 C 24 mp 254.3-254.5.° C.; IRν_(max)(DR)/cm⁻¹ 3443, 3342, 3187, 1647, 1593, 1513, 1414, 1300, 1268and 1225; NMR δ_(H)(400MHz, DMSO) 7.37(2H, s), 6.96(1H, t, J 7.8Hz),6.46(1H, dd, J 1.0, J 8.0Hz), 6.40(2H, d, J 7.5Hz), 6.33(1H, s),5.56(2H, s), 5.2(2H, s), 2.5(3H, s) and 2.44(3H, s). 241 C 17 NMRδ_(H)(400MHz, DMSO) 8.11-8.09(1H, m), 7.89-7.86(1H, dd, J 1.0, 3.5Hz),7.32-7.27(2H, s), 7.22-6.95(1H, t, J 9.0Hz), 6.85-6.83(1H, dd, J 2.0,3.5Hz), 6.35-6.29(2H, m), 5.48-5.46(2H, s) and 5.46-5.44(2H, s);Retention time 1.18 min. 242 B 15 IR ν_(max)(DR)/cm⁻¹ 3850, 3667, 2923,1730, 1601, 1464, 1023, 751 and 593; NMR δ_(H)(400MHz, DMSO) 3.68(1H,dd, J 16.0, 5.5Hz), 3.88(1H, dd, J 16.0, 9.0Hz), 6.05(1H, dd, J 8.5,5.5Hz), 6.84-6.89(1H, m), 7.29(2H, s), 7.57(1H, t, J 7.0Hz), 7.72(1H, d,J 7.5Hz), 7.78-7.87(2H, m), 7.91(1H, d, J 3.5Hz), 8.13 (1H, s). Anal.Calcd for C₁₇H₁₂N₆O₂.0.2 H₂O: C, 60.87; H, 3.72; N, 25.02. Found: C,60.89; H, 3.68; N, 24.85. 243 AF 53 mp > 300° C. dec; IRν_(max)(DR)/cm⁻¹ 3212, 2923, 1642, 1605, 1510, 1461, 1377, 1023 and 757;NMR δ_(H)(400MHz, DMSO) 11.16(1H, br s), 8.12(1H, s), 7.91 (1H, d, J3.5Hz), 7.44-7.36(3H, m), 7.29(1H, s), 6.86(1H, dd, J 3.5, 1.5Hz),6.58(1H, s), 6.42-6.38(1H, m), 5.87(2H, s) and 2.27(3H, s). 244 BB 7 IRν_(max)(Nujol)/cm⁻¹ 3319, 2924, 1646, 1606, 1462; NMR δ_(H)(400MHz,DMSO) 9.54(1H, s), 8.27-8.26(1H, m), 8.12-8.11(1H, m), 7.90(1H, d, J3.5Hz), 7.71(1H, d, J 8.0Hz), 7.32(2H, br s), 7.17-7.15(1H, m),7.11-7.09(1H, m), 6.86-6.85(1H, m), 5.59(2H, s), 2.18(3H, s). 245 B 22IR ν_(max)(Nujol)/cm⁻¹ 3849, 3500, 3298, 3174, 2924, 1698, 1631, 1604,1456, 1379, 1226, 1027, 953 and 753; NMR δ_(H)(400MHz, DMSO) 1.91(3H, d,J 7.0Hz), 6.63(1H, q, J 7.0Hz), 6.84-6.87(1H, m), 7.32(2H, s), 7.54(2H,t, J 8.0Hz), 7.66(1H, tt, J 7.5, 2.0Hz), 7.88(1H, d, J 3.5Hz),7.98-8.03(2H, m), 8.11-8.12 (1H, m). Anal. Calcd for C₁₇H₁₄N₆O₂: C,61.07; H, 4.22; N, 25.12. Found: C, 60.72; H, 4.27; N, 24.75. 246 BE 81IR ν_(max)(Nujol;)/cm⁻¹ 3313, 3189, 2924, 1605, 1461, 1377, 1236, 1026and 762; NMR δ_(H)(400MHz, DMSO) 11.62(1H, br s), 8.11(1H, dd, J 2.0,1.0Hz), 7.90 (1H, d, J 3.5Hz), 7.41(1H, t, J 2.5Hz), 7.37-7.29(3H, m),6.94(1H, d, J 11.0Hz), 6.85(1H, dd, J 3.5, 2.0Hz) 6.52-6.47(1H, m) and5.71(2H, s). 247 B 28 mp 134.5-134.6° C.; IR ν_(max)(Nujol)/cm⁻¹ 3306,3189, 2924, 1635, 1610, 1580; NMR δ_(H)(400MHz, DMSO) 8.13-8.12(1H, m),7.92-7.91(1H, m), 7.79-7.75 (1H, m), 7.35(1H, d, J 8.0Hz), 7.31(2H, brs), 7.03(1H, d, J 7.5Hz), 6.86(1H, dd, J 3.5, 1.5Hz), 5.74(2H, s),4.46(2H, s), 3.65(1H, sept, J 6.0Hz), 1.12(6H, d, J 6.0Hz); Anal. Calcdfor C₁₈H₁₉N₇O₂.1.2 H₂O: C, 55.86; H, 5.57, N, 25.33. Found: C, 55.80; H,5.41; N, 25.05. 248 B 11 mp 158.9.-161.3° C.; IR ν_(max)(Nujol)/cm⁻¹3301, 3185, 2923, 1636, 1611, 1570, 1536, 1501, 1324 and 1210; NMRδ_(H)(400MHz, DMSO) 7.88(1H, d, J 3.0Hz), 7.66(1H, t, J 7.5Hz), 7.27(2H,br s) 7.18(1H, d, J 7.5Hz), 6.89(1H, d, J 7.5Hz), 6.51(1H, dd, J 1.0, J3.5Hz), 5.71(2H, s), 2.69(2H, q, J 7.5Hz), 2.46 (3H, s) and 1.15(3H, J7.5Hz). 249 BE 76 IR ν_(max)(DR;)/cm⁻¹ 3319, 2928, 1605, 1334, 1226,1027, 737 and 528; NMR δ_(H) (400MHz, DMSO) 11.47(1H, s), 8.14-8.09(1H,m) 7.89(1H, d, J 3.5Hz), 7.48(1H, d, J 3.0Hz), 7.38-7.27(3H, m),6.94(1H, d, J 13.0Hz), 6.85(1H, dd, J 3.5, 2.0Hz), 6.52-6.47(1H, m) and5.81(2H, s). 250 BE 68 IR ν_(max)(DR)/cm⁻¹ 3318, 2923, 1640, 1579, 1455,1377, 1079, 1022, 750 and 588; NMR δ_(H)(400MHz, DMSO) 11.13(1H, br s),8.23(1H, s), 8.05-8.04(1H, m), 7.43(1H, d, J 3.5Hz), 7.30(2H, s),7.00(1H, t, J 7.0Hz), 6.90(2H, s), 6.80-6.77 (1H, m), 6.73(1H, d, J6.5Hz), 6.51(1H, s) and 5.63(2H, s). 251 BE 42 mp 294.0-294.2° C.; IRν_(max)(DR)/cm⁻¹ 3498, 3414, 1612, 1318, 1235, 102, 765 and 589; NMRδ_(H)(400MHz, DMSO) 11.24(1H, br s), 8.12(1H, s), 7.91(1H, d, J 3.5Hz),7.53(1H, s), 7.39(1H, t, J 2.5Hz) 7.36-7.26(3H, m), 6.88-6.82 (1H, m),6.43-6.38(1H, m) and 5.76(2H, s) 252 BF 44 mp 200.2-201.2° C. IRν_(max)(DR)/cm⁻¹ 3390, 3205, 2924, 1725, 1648, 1603, 1508, 1423, 1332,1277 and 1158; NMR δ_(H)(400MHz, DMSO) 8.12(1H, s), 7.90(1H, d, J3.5Hz), 7.35-7.25(4H, m), 7.07-6.97(3H, m), 6.86(1H, dd, J 1.5, J3.5Hz), 6.45(2H, t, J 7.5Hz), 6.37(1H, s), 6.32(1H, t, J 6.0Hz),5.49(2H, s) and 4.16(2H, s, J 6.0Hz). 253 B 18 mp 181.8-182.1° C.; IRν_(max)(DR)/cm⁻¹ 3362, 3208, 2988, 1654, 1601, 1513; NMR δ_(H)(400MHz,DMSO) 8.13-8.12(1H, m), 7.91(1H, d, J 3.5Hz), 7.68 (1H, m), 7.29(2H, brs), 6.87-6.85(1H, m), 6.74(1H, d, J 7.5Hz), 6.68(1H, d, J 8.0Hz),5.69(2H, s), 4.07(2H, q, J 7.0Hz), 1.12(3H, t, J 7.0Hz). 254 B 14 mp190.8-190.9° C.; IR ν_(max)(DR)/cm⁻¹ 3514, 3292, 3158, 2984, 1615, 1500;NMR δ_(H)(400MHz, DMSO) 7.88(1H, d, J 3.5Hz), 7.65(1H, dd, J 7.0,8.0Hz), 7.25(2H, br s), 6.72(1H, d, J 7.0Hz), 6.68(1H, d, J 8.0Hz),6.52-6.50(1H, m), 5.67(2H, s), 4.08(2H, q, J 7.0Hz), 2.46(3H, s),1.12(3H, t, J 7.0Hz). 255 BF 20 mp 184.5-184.6° C.; IR ν_(max)(DR)/cm⁻¹3202, 1649, 1601, 1509, 1436, 1331, 1277 and 1221; NMR δ_(H)(400MHz,DMSO) 8.43(1H, d, J 4.89Hz), 8.12(1H, dd, J 0.8, 3.5Hz), 7.91(1H, dd, J0.9, 3.5Hz), 7.65(1H, td, J 1.7, 7.7Hz), 7.30 (2H, br s), 7.25(1H, d, J7.9Hz), 7.15(1H, dd, J 4.9, 7.5Hz), 7.0(1H, t, J 7.8Hz), 6.86(1H, dd, J1.7, 3.5Hz), 6.48-6.36(4H, m), 5.49(2H, s), 4.27(2H, s); Anal. Calcd forC₂₁H₁₈N₈O.0.3 H₂O: C, 62.46; H, 4.64, N, 27.75. Found: C, 62.66; H,4.57; N, 27.36. 256 B 6 Mp 167.6-168.1° C. IR ν_(max)(DR)/cm⁻¹ 3509,3304, 3178, 1609, 1494, 1421, 1325, 1127, 839 and 752. NMR δ_(H)(400MHz,DMSO) 2.05(3H, d, J 7.0Hz), 6.14(1H, q, J 7.0Hz), 6.84-6.88(1H, m),7.30(2H, s), 7.52(2H, d, J 8.5Hz), 7.73(2H, d, J 8.0Hz), 7.91(1H, dd, J3.5, 1.0Hz), 8.11-8.13(1H, m). Anal. Calcd for C₁₇H₁₃N₆F₃O: C, 54.55; H,3.50; N, 22.44. Found: C, 54.52; H, 3.65; N, 22.06. 257 BE 75 IRν_(max)(DR)/cm⁻¹ 3459, 3348, 3187, 2960, 1648, 1513, 1351, 1244, 1011,837 and 759; NMR δ_(H)(400MHz, DMSO) 11.18(1H, br s), 8.11(1H, s),7.89(1H, d, J 3.0Hz), 7.42(1H, d, J 7.5Hz), 7.37-7.26(3H, m), 7.21(1H,d, J 11.0Hz), 6.89-6.81(1H, m), 6.43-6.37(1H, s) and 5.72(2H, s). 258 BE94 mp > 300° C.; dec; IR ν_(max)(DR)/cm⁻¹ 3441, 3318, 2990, 1612, 1285,1083, 839 and 593; NMR δ_(H)(400MHz, DMSO) 11.29(1H, br s), 8.12(1H, s),7.91(1H, d, J 3.5Hz), 7.41-7.29(3H, m), 7.22(1H, dd, J 10.0, 2.5Hz),6.90(1H, dd, J 9.5, 2.5Hz), 6.86(1H, dd, J 3.5, 1.5Hz), 6.30(1H, s) and5.79(2H, s). 259 B 50 mp 228.4-228.5° C.; NMR δ_(H)(400MHz, DMSO)8.13-8.12(1H, m), 7.91 (1H, d, J 3.5Hz), 7.34(2H, br s), 7.18(2H, s),6.87-6.85(1H, m), 5.67(2H, s), 2.22(6H, s). 260 B 8 mp 150.3-151.0° C.IR ν_(max)(DR)/cm⁻¹ 3510, 3306, 3183, 1633, 1495, 1423, 1240, 1029 and753; NMR δ_(H)(400MHz, DMSO) 2.02(3H, d, J 7.0Hz), 6.05 (1H, q, J7.0Hz), 6.83-6.88(1H, m), 7.10-7.22(3H, m), 7.30(2H, s), 7.40 (1H, dt, J8.0, 6.5Hz), 7.91(1H, dd, J 3.5, 1.0Hz), 8.10-8.13(1H, m). Anal. Calcdfor C₁₆H₁₃N₆OF.0.25 H₂O: C, 58.44; H, 4.14; N, 25.56. Found: C, 58.48;H, 3.98; N, 25.40. 261 BE 91 IR ν_(max)(DR)/cm⁻¹ 3472, 3318, 3184, 2922,1651, 1595, 1478, 1417, 1329, 1218, 1097, 1015, 870, 767 and 545; NMRδ_(H)(400MHz, DMSO) 11.50(1H, s), 8.11 (1H, s), 7.90(1H, d, J 3.5Hz),7.47(1H, s), 7.42(1H, t, J 3.0Hz), 7.33(2H, s), 7.19(1H, s),6.86-6.84(1H, m), 6.53-6.51(1H, m), 5.71(2H, s). 262 C 34 mp250.1-261.3° C.; IR ν_(max)(DR)/cm⁻¹ 3325, 3205, 2968, 1603, 1488; NMRδ_(H) (400MHz, DMSO) 8.11-8.10(1H, m), 7.89-7.87(1H, m), 7.28(2H, br s),6.85-6.83 (1H, m), 6.81(2H, s), 5.40(2H, s), 4.56(2H, br s), 2.03(6H,s). 263 K 72 IR ν_(max)(DR)/cm⁻¹ 2825, 2021, 1645, 1453, 1394, 1286,1171, 1030, 779 and 619; NMR δ_(H)(400MHz, DMSO) 2.02(3H, d, J 7.0Hz),6.07(1H, q, J 7.0Hz), 6.85-6.88(1H, m), 7.13-7.18(1H, m), 7.25(1H, d, J8.5Hz), 7.36(1H, d, J 8.0Hz), 7.47(1H, t, J 7.5Hz), 7.92(1H, d, J3.5Hz), 8.12-8.14(1H, m). Anal. Calcd for C₁₆H₁₅N₇O.2HCl.0.8 H₂O: C,47.02; H, 4.59; N, 23.99. Found: C, 46.87; H, 4.43; N, 23.71. 264 B 26mp 162.0-162.6° C.; IR ν_(max)(DR)/cm⁻¹ 3319, 3206, 2932, 1644, 1505;NMR δ_(H) (400MHz, DMSO) 8.13-8.12(1H, m), 7.92-7.91(1H, m),7.68-7.64(1H, m), 7.31(2H, br s), 7.21(1H, d, J 7.5Hz), 6.92(1H, d, J8.0Hz), 6.86(1H, dd, J 3.5, 1.5Hz), 5.74(2H, s), 3.58(2H, t, J 6.5Hz),3.16(3H, s), 2.84(2H, t, J 6.5Hz); M/Z 352(M+H)⁺. 265 B 15 NMRδ_(H)(400MHz, DMSO) 8.12-8.11(1H, m), 7.92-7.90(1H, m), 7.47(1H, d, J8.0Hz), 7.28(2H, br s), 6.91(1H, d, J 8.0Hz), 6.86(1H, dd, J 2.0,3.5Hz), 5.73-5.69(1H, m), 2.60-2.46(2H, m), 2.39(3H, s), 2.20(3H, s),0.87(3H, t, J 7.0Hz); M/Z 350(M+H)⁺. 266 AK 99 NMR δ_(H)(400MHz, DMSO)8.22-8.17(2H, m), 7.94(1H, d, J 2.01Hz), 7.73-7.63 (2H, m), 7.37(1H, d,J 2.5Hz) and 5.86(2H, s); M/Z 338(M+H)⁺; Retention time 1.74 min. 267 B58 mp 255.6-255.7° C.; IR ν_(max)(DR)/cm⁻¹ 3512, 3294, 3179, 2960, 2692,1745, 1638, 1432 and 1371; NMR δ_(H)(400MHz, DMSO) 7.88(1H, d, J3.51Hz), 7.81 (1H, dd, J 1.0, J 8.0Hz), 7.46-7.29(2H, br s), 7.40(1H, t,J 7.8Hz), 7.23(1H, d, J 8.0Hz), 6.51(1H, dd, J 1.0, 3.5Hz), 5.78(2H, s)and 2.46(6H, s). 268 B 40 mp 248.1-249.0° C. IR ν_(max)(DR)/cm⁻¹ 3507,3308, 3190, 2952, 1626, 1571, 1519, 1434, 1348 and 1291; NMRδ_(H)(400MHz, DMSO) 8.22(2H, d, J 8.5Hz), 7.89(1H, d, J 3.5Hz), 7.49(2H,d, J 9.0Hz), 7.36(2H, br s), 6.52(1H, dd, J 1.0, 3.5Hz), 5.83(2H, s) and2.46(3H, s). 269 B 18 NMR δ_(H)(400MHz, DMSO) 8.14-8.12(1H, m),7.92-7.90(1H, dd, J 1.0, 3.5Hz), 7.42-7.34(2H, s), 7.26-7.25(4H, s),6.87-6.85(1H, dd, J 1.5, 3.5Hz), 5.66-5.64(2H, s), 3.15-3.13(3H, s) and1.38-1.36(9H, s). 270 H 46 NMR δ_(H)(400MHz, DMSO) 8.22-8.13(2H, m),7.75-7.65(3H, m), 7.59(1H, dd, J 1.5, J 3.0Hz), 7.34(2H, br s), 6.96(1H,dd, J 1.5, J 3.5Hz), 6.45(1H, t, J 3.2Hz), 5.85(2H, s) and 1.22(9H, s);M/Z 437(M+H)⁺; Retention time 4.36 min. 271 Q 40 NMR δ_(H)(400MHz, DMSO)8.21-8.17(2H, m), 7.71-7.63(2H, m), 7.48(2H, br s), 5.87(2H, s),2.50(3H, s) and 2.44(3H, s); M/Z 383(M+H)⁺; Retention time 3.69 min. 272B NMR δ_(H)(400MHz, DMSO) 8.18(1H, dd, J 9.6, 2.0Hz), 8.13(1H, d, J1.6Hz), 8.05(1H, dd, J 8.4, 2.4Hz), 7.90(1H, d, J 3.2Hz), 7.45(1H, t, J8.0Hz), 7.38 (2H, br s), 6.86(1H, dd, J 3.6, 2.0Hz) and 5.84(2H, s). 273B NMR δ_(H)(400MHz, DMSO) 8.13-8.09(1H, m), 7.89(1H, d, J 3.5Hz), 7.66(1H, d, J 3.5Hz), 7.39(1H, s), 7.29(2H, br s), 6.85(1H, dd, J 3.5,2.0Hz), 6.68 (1H, d, J 3.5Hz), 6.65(1H, s), 2.27(3H, s) and 1.52(9H, s).274 BA 99 IR ν_(max)(Nujol)/cm⁻¹ 3313, 2923, 1693, 1603; NMRδ_(H)(400MHz, DMSO) 8.78 (1H, br s), 8.12-8.11(1H, m), 7.90(1H, d, J3.5Hz), 7.34-7.31(3H, m), 7.13-7.12 (1H, m), 7.08-7.05(1H, m),6.86-6.85(1H, m), 5.58(2H, s), 4.08(2H, q, J 7.0Hz), 2.16(3H, s),1.21(3H, t, J 7.0Hz).

[0445] Adenosine Receptor Binding

[0446] Binding Affinities at hA_(2A) Receptors

[0447] The compounds were examined in an assay measuring in vitrobinding to human adenosine A_(2A) receptors by determining thedisplacement of the adenosine A_(2A) receptor selective radioligand[³H]-CGS 21680 using standard techniques. The results are summarised inTable 3. TABLE 3 Example K_(i) (nM) Example 3 3 Example 4 4 Example 5 3Example 8 3 Example 11 2 Example 12 7 Example 13 2 Example 15 4 Example41 2 Example 57 2 Example 78 3 Example 92 2 Example 107 2 Example 120 1Example 149 1 Example 156 2 Example 169 2 Example 188 1 Example 202 1Example 209 1 Example 221 2 Example 233 4 Example 255 4

[0448] Evaluation of Potential Anti-Parkinsonian Activity In Vivo

[0449] Haloperidol-Induced Hypolocomotion Model

[0450] It has previously been demonstrated that adenosine antagonists,such as theophylline, can reverse the behavioural depressant effects ofdopamine antagonists, such as haloperidol, in rodents (Mandhane S. N. etal., Adenosine A₂ receptors modulate haloperidol-induced catalepsy inrats. Eur. J. Pharmacol. 1997, 328, 135-141). This approach is alsoconsidered a valid method for screening drugs with potentialantiparkinsonian effects. Thus, the ability of novel adenosineantagonists to block haloperidol-induced deficits in locomotor activityin mice can be used to assess both in vivo and potentialantiparkinsonian efficacy.

[0451] Method

[0452] Female TO mice (25-30 g) obtained from TUCK, UK, are used for allexperiments. Animals are housed in groups of 8 [cage size−40 (width)×40(length)×20 ( height)cm] under 12 hr light/dark cycle (lights on 08:00hr), in a temperature (20≅2° C.) and humidity (55±15%) controlledenvironment. Animals have free access to food and water, and are allowedat least 7 days to acclimatize after delivery before experimental use.

[0453] Drugs

[0454] Liquid injectable haloperidol (1 ml Serenance ampoules from BakerNorton, Harlow, Essex, each containing haloperidol BP 5 mg, batch #P424) are diluted to a final concentration of 0.02 mg/ml using saline.Test compounds are typically prepared as aqueous suspensions in 8%Tween. All compounds are administered intraperitoneally in a volume of10 ml/kg.

[0455] Procedure

[0456] 1.5 hours before testing, mice are administered 0.2 mg/kghaloperidol, a dose that reduces baseline locomotor activity by at least50%. Test substances are typically administered 5-60 minutes prior totesting. The animals are then placed individually into clean, clearpolycarbonate cages [20 (width)×40 (length)×20 (height) cm, with a flatperforated, Perspex lid]. Horizontal locomotor activity is determined byplacing the cages within a frame containing a 3×6 array of photocellslinked to a computer, which tabulates beam breaks. Mice are leftundisturbed to explore for 1 hour, and the number of beams breaks madeduring this period serves as a record of locomotor activity which iscompared with data for control animals for statistically significantdifferences.

[0457] 6-OHDA Model

[0458] Parkinson's disease is a progressive neurodegenerative disordercharacterised by symptoms of muscle rigidity, tremor, paucity ofmovement (hypokinesia), and postural instability. It has beenestablished for some time that the primary deficit in PD is a loss ofdopaminergic neurones in the substantia nigra which project to thestriatum, and indeed a substantial proportion of striatal dopamine islost (ca 80-85%) before symptoms are observed. The loss of striataldopamine results in abnormal activity of the basal ganglia, a series ofnuclei which regulate smooth and well co-ordinated movement (Blandini F.et al., Glutamate and Parkinson's Disease. Mol. Neurobiol. 1996, 12,73-94). The neurochemical deficits seen in Parkinson's disease can bereproduced by local injection of the dopaminergic neurotoxin6-hydroxydopamine into brain regions containing either the cell bodiesor axonal fibres of the nigrostriatal neurones.

[0459] By unilaterally lesioning the nigrostriatal pathway on onlyone-side of the brain, a behavioural asymmetry in movement inhibition isobserved. Although unilaterally-lesioned animals are still mobile andcapable of self maintenance, the remaining dopamine-sensitive neuroneson the lesioned side become supersenstive to stimulation. This isdemonstrated by the observation that following systemic administrationof dopamine agonists, such as apomorphine, animals show apronouncedrotation in a direction contralateral to the side of lesioning. Theability of compounds to induce contralateral rotations in 6-OHDAlesioned rats has proven to be a sensitive model to predict drugefficacy in the treatment of Parkinson's Disease.

[0460] Animals

[0461] Male Sprague-Dawley rats, obtained from Charles River, are usedfor all experiments. Animals are housed in groups of 5 under 12 hrlight/dark cycle (lights on 08:00 hr), in a temperature (20±2° C.) andhumidity (55±15%) controlled environment. Animals have free access tofood and water, and are allowed at least 7 days to acclimatize afterdelivery before experimental use.

[0462] Drugs

[0463] Ascorbic acid, desipramine, 6-OHDA and apomorphine(Sigma-Aldrich, Poole, UK). 6-OHDA is freshly prepared as a solution in0.2% ascorbate at a concentration of 4 mg/mL prior to surgery.Desipramine is dissolved in warm saline, and administered in a volume of1 ml/kg. Apomorphine is dissolved in 0.02% ascorbate and administered ina volume of 2 ml/kg. Test compounds are suspended in 8% Tween andinjected in a volume of 2 ml/kg.

[0464] Surgery

[0465] 15 minutes prior to surgery, animals are given an intraperitonealinjection of the noradrenergic uptake inhibitor desipramine (25 mg/kg)to prevent damage to nondopamine neurones. Animals are then placed in ananaesthetic chamber. and anaesthetised using a mixture of oxygen andisoflurane. Once unconscious, the animals are transferred to astereotaxic frame, where anaesthesia is maintained through a mask. Thetop of the animal's head is shaved and sterilised using an iodinesolution. Once dry, a 2 cm long incision is made along the midline ofthe scalp and the skin retracted and clipped back to expose the skull. Asmall hole is then drilled through the skill above the injection site.In order to lesion the nigrostriatal pathway, the injection cannula isslowly lowered to position above the right medial forebrain bundle at−3.2 mm anterior posterior, −1.5 mm medial lateral from bregma, and to adepth of 7.2 mm below the duramater. 2 minutes after lowing the cannula,2 VAL of 6-OHDA is infused at a rate of 0.5 μl/min over 4 minutes,yeilding a final dose of 8 μg. The cannula is then left in place for afurther 5 minutes to facilitate diffusion before being slowly withdrawn.The skin is then sutured shut using Ethicon W501 Mersilk, and the animalremoved from the strereotaxic frame and returned to its homecage. Therats are allowed 2 weeks to recover from surgery before behaviouraltesting.

[0466] Apparatus

[0467] Rotational behaviour is measured using an eight station rotametersystem provided by Med Associates, San Diego, USA. Each station iscomprised of a stainless steel bowl (45 cm diameter×15 cm high) enclosedin a transparent Plexiglas cover running around the edge of the bowl,and extending to a height of 29 cm. To assess rotation, rats are placedin cloth jacket attached to a spring tether connected to opticalrotameter positioned above the bowl, which assesses movement to the leftor right either as partial (45°) or full (360°) rotations. All eightstations are interfaced to a computer that tabulated data.

[0468] Procedure

[0469] To reduce stress during drug testing, rats are initiallyhabituated to the apparatus for 15 minutes on four consecutive days. Onthe test day, rats are given an intraperitoneal injection of testcompound 30 minutes prior to testing. Immediately prior to testing,animals are given a subcutaneous injection of a subthreshold dose ofapomorphine, then placed in the harness and the number of rotationsrecorded for one hour. The total number of full contralatral rotationsduring the hour test period serves as an index of antiparkinsonian drugefficacy.

1. The use of a compound of formula (I):

wherein R₁ is selected from H, alkyl, aryl, alkoxy, aryloxy, alkylthio,arylthio, halogen, CN, NR₅R₆, NR₄COR₅, NR₄CONR₅R₆, NR₄CO₂R₇ andNR₄SO₂R₇; R₂ is selected from aryl attached via an unsaturated carbon;R₃ is selected from H, alkyl, COR₅, CO₂R₇, CONR₅R₆, CONR₄NR₅R₆ andSO₂R₇; R_(4,) R₅ and R₆ are independently selected from H, alkyl andaryl or where R₅ and R₆ are in an NR₅R₆ group, R₅ and R₆ may be linkedto form a heterocyclic group, or where R_(4,) R₅ and R₆ are in a(CONR₄NR₅R₆) group, R₄ and R₅ may be linked to form a heterocyclicgroup; and R₇ is selected from alkyl and aryl, or a pharmaceuticallyacceptable salt thereof or prodrug thereof, in the manufacture of amedicament for the treatment or prevention of a disorder in which theblocking of purine receptors may be beneficial.
 2. Use according toclaim 1 wherein R₁ is selected from alkyl, aryl, alkoxy, aryloxy,alkylthio, arylthio, halogen, CN, NR₅R₆, NR₄COR₅, NR₄CONR₅R₆, NR₄CO₂R₇and NR₄SO₂R₇.
 3. Use according to claim 1 wherein R₁ is selected fromalkyl, alkoxy, alkylthio, NR₅R₆, NR₄COR₅, NR₄CONR₅R₆, NR₄CO₂R₇ andNR₄SO₂R₇.
 4. Use according to claim 1 wherein R₁ is selected from NR₅R₆,NR₄COR₅, NR₄CONR₅R₆, NR₄CO₂R₇ and NR₄SO₂R₇.
 5. Use according to claim 1wherein R₁ is selected from NR₅R₆.
 6. Use according to claim 1 whereinR₁ is NH₂.
 7. Use according to claim 1 wherein R₁ is selected fromhaloalkyl and arylalkyl.
 8. Use according to any preceding claim whereinR₂ is not ortho,ortho-disubstituted.
 9. Use according to any precedingclaim wherein R₂ is not substituted at either ortho position.
 10. Useaccording to any preceding claim wherein R₂ is a heteroaryl group. 11.Use according to claim 10 wherein R₂ is a heteroaryl group which isattached to the pyrimidine ring of formula (I) such that a heteroatom isadjacent to the unsaturated carbon atom attached to said pyrimidinering.
 12. Use according to claim 10 or 11 wherein R₂ is an N, O orS-containing heteroaryl group.
 13. Use according to any of claims 10 to12 wherein R₂ is selected from furyl, thienyl, pyridyl, thiazolyl,pyrazolyl, triazolyl, pyrrolyl and oxazolyl.
 14. Use according to any ofclaims 10 to 12 wherein R₂ is selected from 2-furyl, 2-thienyl,2-thiazolyl, 2-pyridyl, 3-pyrazolyl, 2-pyrrolyl, 4-triazolyl and5-oxazolyl.
 15. Use according to any of claims 10 to 12 wherein R₂ isselected from furyl, thienyl, pyridyl, thiazolyl and pyrazolyl.
 16. Useaccording to any of claims 10 to 12 wherein R₂ is selected from 2-furyl,2-thienyl, 2-thiazolyl, 2-pyridyl and 3-pyrazolyl.
 17. Use according toany of claims 10 to 12 wherein R₂ is 2-furyl.
 18. Use according to anyof claims 1 to 9 wherein R₂ is phenyl.
 19. Use according to anypreceding claim wherein R₃ is selected from H and substituted alkyl. 20.Use according to claim 19 wherein R₃ is selected from alkyl substitutedby aryl, cycloalkyl, non-aromatic heterocyclyl, CN, CO₂R₅,CONR₅R₆,CONR₄NR₅R₆ or C(═NR₄)NR₅R₆.
 21. Use according to claim 19wherein R₃ is selected from alkyl substituted by aryl.
 22. Use accordingto claim 21 wherein R₃ is selected from (CR₉R₁₀)_(n)R₁₁ wherein n is 1to 6, R₉ and R₁₀ are independently selected from H, alkyl and aryl, andR₁₁ is selected from the group consisting of substituted aryl (includingheteroaryl) groups.
 23. Use according to claim 22 wherein R₁₁ isselected from mono-, di- or tri-substituted aryl groups represented bythe formula Ar(R₁₂)_(a)(R₁₃)_(b)(R₁₄)_(c) wherein Ar is an aryl group;wherein R₁₂, R₁₃ and R₁₄ are substituent group(s), the same ordifferent; and wherein a, b and c are 0 or 1 such that a+b+c≧1.
 24. Ause according to claim 22 or 23 wherein n is 1 to
 3. 25. A use accordingto claim 22 or 23 wherein n is
 1. 26. A use according to any of claims22 to 25 wherein the or each R₉ and R₁₀ are selected from H and alkyl.27. A use according to any of claims 22 to 25 wherein at least one ofthe or each R₉ and R₁₀ is H.
 28. A use according to any of claims 22 to25 wherein both the or each R₉ and R₁₀ are H.
 29. Use according to anyof claims 23 to 28 wherein R₁₂, R₁₃ and R₁₄ are independently selectedfrom NR₅R₆, alkyl, alkoxy, halogen, NO₂, CN, hydroxy, NHOH, CHO,CONR₅R₆, CO₂R₅, NR₄COR₅, NR₄CO₂R_(7,) NR₄SO₂R₇, OCO₂R₇ and aryl.
 30. Useaccording to any of claims 23 to 28 wherein R₁₂, R₁₃ and R₁₄ areindependently selected from NR₅R₆, alkyl and halogen.
 31. Use accordingto claim 29 or 30 wherein R₁₂, R₁₃ and R₁₄ are independently selectedfrom alkyl, and said alkyl is substituted alkyl and is selected fromalkoxyalkyl, hydroxyalkyl, aminoalkyl and haloalkyl.
 32. Use accordingto claim 29 or 30 wherein R₁₂, R₁₃ and R₁₄ are independently selectedfrom unsubstituted alkyl, NH₂ and fluoro.
 33. A use according to any ofclaims 22 to 32 wherein said substituted aryl group R₁₁ or Ar isselected from phenyl, pyridyl, indolyl, furyl, thienyl, isoindolyl,indolinyl, isoxazolyl, oxazolyl, thiazolyl, pyrazinyl, pyrimidinyl,quinolinyl, benzoxadiazolyl, benzothiadiazolyl, benzotriazolyl,indazolyl, benzodioxolyl and dihydrobenzofurayl.
 34. Use according toany of claims 22 to 32 wherein said substituted aryl group R₁₁ or Ar isselected from phenyl, pyridyl, indolyl, furyl and thienyl.
 35. Useaccording to claim 34 wherein said substituted aryl group R₁₁ or Ar isselected from phenyl, thienyl, furyl and pyridyl.
 36. Use according toclaim 34 wherein said substituted aryl group R₁₁ or Ar is selected fromphenyl, 2-thienyl, 2-furyl and 2-pyridyl.
 37. Use according to any ofclaims 1 to 18 wherein R₃ is selected from (CR₉R₁₀)_(n)R₈ wherein n is 1to 6, R₉ and R₁₀ are independently selected from H alkyl and aryl, andR₈ is selected from cycloalkyl, non-aromatic heterocyclic, CN, CO₂R₅,CONR₅R₆, CONR₄NR₅R₆ and C(═NR₄)NR₅R₆.
 38. Use according to claim 37wherein n, R₉ and R₁₀ are as set out in any claims 24 to 28
 39. Useaccording to claim 37 wherein R is selected from CONR₅R₆, R₅ is hydrogenand R₆ is selected from unsubstituted alkyl and arylalkyl.
 40. Useaccording to any of claims 1 to 18 wherein R₃ is selected from CONR₅R₆,R₅ is H and R₆ is selected from arylalkyl, preferably arylmethyl. 41.Use according to claim 1 wherein the compound is selected from:7-(2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amineN,N-bis(2-fluorobenzyl)-3-(2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5d]pyrimidine-5-amine7-(2-furyl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(3-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrinidine-5-aminemethyl3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)methylbenzoate3-(3,5-dimethoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(5-chloro-2-thienyl)methyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amineN-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)methyl)phenyl-(1-methyl-1H-imidazol-4-yl)sulphonamide5-amino-N-benzyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrinmidin-3-ylcarboxamide7-(2-furyl)-3-(3-methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(2-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amineethyl 5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylacetate3-(3yanobenzyl)7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrmidine-5-amine7-(2-furyl)-3-(3-(3-pyridyl)propyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(3-trifluoromethylbenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(3-hydroxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(5-methyl-2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2-fluorobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(1H-pyrazol-3-yl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2-fluorobenzyl)-7-(5-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(3-methylbenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(3-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)acetic acid3-(3-chlorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2-fluorobenzyl)-7-(1H-pyrazol-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrinidine-5-amine7-(2-furyl)-3-methyl-3H-[1,2,3]triazolo[4,5d]pyrimidine-5-amine(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)acetamide(5-amino-7-(2-firyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-N-(3-chlorophenyl)acetamide7-(2-furyl)-3-(6-methoxy-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrinidine-5-amine7-(2-furyl)-3-(2-thienylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2-fluorobenzyl)-7-(2-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2-fluorobenzyl)-7-(2-thienyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(3-aminobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(6-methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrinidine-5-amine3-(2-fluorobenzyl)-7-(5-methyl-2-thiazolyl)-3H-[1,2,3]triazolo[4,5d]pyrimidine-5-aminetert-butylN-(3-(5-amino7-(2-furyl)-3H-[1,2,3]triazolo[4,5d]pyrimidine-3-ylmethyl)benzyl)carbamate3-(2,5-dimethoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5d]pyrimidine-5-amine3-(2,6-difluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2-fluorobenzyl)-7-(4-methyl-2-thiazolyl)-3H-[1,2,3]triazolo[4,5]pyrimidine-5-amine7-(2-thienyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine6-chloro-N-(7-(2-firyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)pyridine-3-carboxamide3-(3-nitrobenzyl)-7-(5-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(3-aminomethylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5d]pyrmidine-5-amine3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5d]pyrimidin3-ylmethyl)-N,N-dimethylbenzamide3-(3-aminobenzyl)-7-(2-thienyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-N-methylbenzamide3-(3-aminobenzyl)-7-(5-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2-fluoro-5-methoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-N-(2-pyridyl)acetamide(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-N-(2-pyridylmethyl)acetamide(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-N-phenylacetamide3-(3,5-dinitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(5-methyl-2-furyl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2,3-difluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2,4-difluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrinidine-5-amine7-(5-methyl-2-furyl)-3-(6-methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2,6-difluorobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrmidine-5-amine7-(5-methyl-2-furyl)-3-(2-thienylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(3-chlorobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(4-methoxy-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(2-methylbenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2,5-difluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(2-methoxy-5-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine3-(5-amino-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrmidine-3-ylmethyl)-N-methylbenzamideN-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzyl)acetamide3-(2-fluorobenzyl)-7-(5-oxazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(4-chloro-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrmidine-5-amine3-(6-fluoro-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2-methoxybenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-aminetert-butylN-(3-(5-amino-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)benzyl)carbamate3-(2-aminobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-aminehydrochloride3-(3,5-diaminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrinidine-5-amine3-(3-aminomethylbenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-aminehydrochloride7-(2-furyl)-3-(2-methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2-fluoro-5-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(5-amino-2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2-fluorobenzyl)-7-(1H-triazolo4yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(6-chloro-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(5-methyl-2-furyl)-3-(6-phenyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(3-aminobenzyl)-7-(2-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(5-amino-2-fluorobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-aminehydrochlorideN-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzyl)-3-methylbenzamide7-(5-methyl-2-furyl)-3-(4-nitro-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(4-hydroxylamino-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(2-methyl-3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(3-amino-2-methylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(3-amino-4methylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(3,5-dimethylisoxazol4-ylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5amine7-(2-furyl)-3-(3-methyl-2-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-cyclohexylmethyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(3-methylnitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(3-methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(5-methyl-2-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(4amino-3-methylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzoicacid3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzamide7-(2-furyl)-3-(2-methylthiazolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrmidine-5-amine3-(3-aminomethylbenzyl)-7-(1H-pyrazol-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-N-isopropyl-N-methylbenzamide3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-N-isopropylbenzamide3-(2-amino-5-methylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(4-cyano-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(5-methyl-2-pyrazinylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(8-quinolinylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(2-phenylthiazol4-ylmethyl)3H-[I,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(4-methyl-2-thiazolyl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(4-chloro-3-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(1,2,5-benzoxadiazol-5-yl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(6-methoxymethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5amine3-benzyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(3-amino4chlorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(4-nitro-2-pyridyhnethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(4-hydroxylamino-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5amine7-(2-furyl)-3-(6methyl-4-nitro-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(4-hydroxylamino-6-methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(4chloro-2-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2-amino-4-chlorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(4-cyanobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(3,4-dimethoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-aminetrifluoroacetate salt7-(5-methyl-2-furyl)-3-(3-methyl-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(4-amino-3-methylbenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(5-methyl-3-oxazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrinidine-5-amine7-(2-furyl)-3-(3-methyl4pyridylmethyl)-3H-[1,2,3]triazolo[4,5)pyrimidine-5-amine3-(1,2,5-benzothiadiazol4-ylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(2-pyrazinylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrinidine-5-amine3-(4-fluoro-3-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrinidine-5-amine3-(3-nitrobenzyl)-7-phenyl-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(4-methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrinidine-5-aminetert-butylN-(2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-4-pyridylmethyl)carbamate7-(2-furyl)-3-(3-methoxy-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(6-ethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2-ethylpyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrinidine-5-aminetert-butyl7-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)indole-1-carboxylatetert-butyl4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)indole-1-carboxylate7-(2-furyl)-3-(4-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrinidine-5-aminetert-butylN-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)benzyl)carbamate3-(4aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo4,5-d]pyrimidine-5-aminetert-butyl5-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)indole-1-carboxylatetert-butylN-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrmidine-3-ylmethyl)-2-fluorophenyl)carbamate3-(4-aminomethylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(5-ethyl-2-furyl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-aminetert-butyl6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrinidine-3-ylmethyl)indole-1-carboxylate3-(4-amino-3-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-aminetert-butyl(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-3,5-difluorophenyl)carbonate3-(2,6-difluoro-4-hydroxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(3-aminobenzyl)7-(5-ethyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(3-aminobenzyl)-7-phenyl-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(6-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(5-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyriridine-5-amine7-(2-furyl)-3-(7-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(5-fluoro-2-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2,6-difluoro4-methoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-aminetert-butylN-(2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)benzyl)carbamate3-(1H-benzotriazol-5-ylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-dpyrimidine-5-amine7-(2-furyl)-3-(2-methylnitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amineN-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)phenylacetamide3-(2-amninomethylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(3-(N,N-dimethylamine)benzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5amine3-(4-difluoromethoxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrinidine-5-amine7-(2-furyl)-3-(6-phthalimidomethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine5-amine3-(3-aminofluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2,3dihydrobenzofuran-5-ylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(5-bromo-2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine7-(2-furyl)-3-(2,3,5-trifluorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2-fluoro-5-iodobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(2-furylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2-amino-5-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-aminetert-butyl(5-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-2-nitrophenyl)carbonate3-(4-amino-3-hydroxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(4-amino-3-fluorobenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(3-aminobenzyl)-7-(1H-pyrazol-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(3-hydroxy-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amineN-(6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2-pyridylmethyl)acetamideN-(2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)benzyl)acetamide7-(2-furyl)-3-(3-thienylmethyl)-3H-[1,2,3]triazolo(4,5-d]pyrimidine-5-amine3-(3-amino-2-methylbenzyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(3-methyl-2-thienyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(6-allyloxymethyl-2-pyridylmethyl)-N,N-diallyl-7-(2-furyl)-3H-[1,2,3]triazolo[4,5d]pyrimidine-5-amine3-(6-methoxymethyl-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5d]pyrimidine-5-amine3-(4-aminobenzyl)-7-(5-methyl-2-furyl)3H-[I,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(6-allyloxymethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5amine3-(6-allyloxymethyl-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(3-isopropyl4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(quinolin-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(4-(N-methylamino)benzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-(6-methyl-2-pyridyl)propanone3-(3-aminobenzyl)-7-(1H-pyrrole-2-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(3-nitrobenzyl)-7-(2-pyridyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amineN-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)acetamide7-(2-furyl)-3-(4-nitro-2-(2-trimethylsilylethoxy)methoxybenzyl)-3H-[1,2,3]triazolo[4,5d]pyrimidine-5-amine3-(3-ethyl-4-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(2-(2-thienylmethyl))-3H-[1,2,3]triazolo[4,5-d]pyrmidine-5-amine7-(2-furyl)-3-(6-isopropyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(1-(2H-tetrahyropyran-2-yl)indazol-5-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(4,6-diisopropyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(5-indazolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(2-hydroxy4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5d]pyrimidine-5-amine7-(2-furyl)-3-(6-vinyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-aminetert-butyl5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-carboxylatetert-butyl3-(5-amino-7-(2-firyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)indole-1-carboxylate6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)pyridine-2-carboxaldehydetert-butyl2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5d]pyrimidine-3-ylmethyl)indole-1-caboxylate3-(2-indolylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrmidine-5-amine3-(5-ethyl-2-thienybnethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(3,4-methylenedioxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(4-amino-3-ethylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-phenylethanoneN-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-methyl)phenyl)thiophene-2-carboxamide7-(2-furyl)-3-(6-hydroxymethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-aminehydrochlorideN-(3-(5-amino-7-(2-firyl)-3H-[1,2,3]triazolo[4,5-d]pyrmidine-3-methyl)phenyl)-3,3-dimethylbutanamideN-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-methyl)phenyl)cyclopropanecarboxamide7-(2-furyl)-3-(6-n-propyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(6-isobutyloxymethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(6-bromomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5amine3-(4-amino-3-isopropylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(6-aminomethyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(4-hydroxybenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-(4-nitrophenyl)ethanone4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylacetyl)-benzonitrileN-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)propanesulphonamideN-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5]pyrimidin-3-ylmethyl)phenyl)-5-amine7-(2-furyl)-3-(6-(N-methylamino)methyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5d]pyrimidine-5-aminehydrochloride 2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-(4-(N,N-diethylamino)phenyl)ethanone7-(2-furyl)-3-(6-isopropyl-3-pyridylmethyl)-3H-[l,2,3]triazolo[4,5-d]pyrimidine-5-amine2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-(4-methoxyphenyl)ethanonetert-butyl7-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-5-chloroindole-1-carboxylate3-(5-chloro-7-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amineN-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)-3,5-dimethylisoxazol-4-ylsulphonamide3-(6-(N,N-dimethylamine)methyl-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(6-methylthiomethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine5-amine2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-(2-nitrophenyl)ethanoneN-(3-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)phenyl)-1,2-dimethyl-1H-imidazol-4-ylsulphonamideN,N-bis(6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2-pyridylmethyl)methanesulphonamide7-(2-furyl)-3-(6-methylsulphonylmethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amineN-(6-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2-pyridylmethyl)-N-methylmethanesulphonamide3-(3-aminobenzyl)-7-(4,5-dimethyl-2-thiazolyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5amine3-(4-amino-2-fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-indanone7-(2-furyl)-3-(5-methyl-7-indolylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amineN-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-ylmethyl)-2-methylphenyl)formamide2-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-1-phenylpropanone3-(7-fluoro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrinidine-5-amine7-(2-furyl)-3-(6-isopropoxymethyl-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine5-amine3-(6-ethyl-2-pyridyhmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(4-chloro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(7-bromo-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(6-chloro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(3-(4-fluorobenzylamino)benzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(6-ethoxy-2-pyridylmethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(6-ethoxy-2-pyridylmethyl)-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(3-(2-pyridylmethylamino)benzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(1-(4-trifluoromethylphenyl)ethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5amine3-(6-fluoro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(5-fluoro-2-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(3,5-dimethyl4-nitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(1-(3-fluorophenyl)ethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(7-chloro-5-indolyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(4-amino-3,5-dimethylbenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(1-(3-aminophenyl)ethyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine7-(2-furyl)-3-(6-(2-methoxyethyl)-2-pyridylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine5-amine7-(2-furyl)-3-(l-(5,6methyl-2-pyridyl)propyl)-3H-[I,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(3-nitrobenzyl)-7-(1H-pyrazol-3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-aminehydrochloride7-(5-methyl-2-furyl)-3-(2-methyl-3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5amine7-(5-methyl-2-furyl)-3-(nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-aminetert-butylN-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)phenyl)-N-methylcarbamatetert-butyl2-(5-amino-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyimidin-7-yl)pyrrole-1-carboxylate7-(4,5-dimethylthiazol-2-yl)-3-(3-nitrobenzyl)-3H-[l,2,3]triazolo[4,5-d]pyrimidine-5-amine3-(2-fluoronitrobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-aminetert-butyl7-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-3-ylmethyl)-5-methylindole-1-carboxylate,and ethylN-(4-(5-amino-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)methyl)-2-methylphenyl)carbamate.42. Use according to claim 1 wherein the compound is selected from:3-(2fluorobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine;7-(2-furyl)-3-(3-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine;3-(3-aminobenzyl)-7-(2-furyl)-3H-[l,2,3]triazolo[4,5-d]pyrimidine-5-amine;3-(3-aminobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine;7-(2-furyl)-3-(3-methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine;7-(2-furyl)-3-(2-nitrobenzyl)-3H-[2,3]triazolo[4,5-d]pyrimidine-5-amine;3-(2-aminobenzyl)-7-(2-furyl)3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine;and3-(3-cyanobenzyl)-7-(2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine-5-amine.43. A method of treating or preventing a disorder in which the blockingof purine receptors may be beneficial comprising administration to asubject in need of such treatment an effective dose of a compound as setout in any one of claims 1 to 42 or a pharmaceutically acceptable saltthereof.
 44. A use or method according to any preceding claim whereinthe disorder is caused by the hyper functioning of purine receptors. 45.A use or method according to any preceding claim wherein the purinereceptors are adenosine receptors.
 46. A use or method according toclaim 45 wherein the adenosine receptors are A_(2A) receptors.
 47. A useor method according to any preceding claim wherein the disorder is amovement disorder.
 48. A use or method according to claim 47 wherein themovement disorder is Parkinson's disease.
 49. A use or method accordingto claim 48 for treatment of drug-induced Parkinsonism,post-encephalitic Parkinsonism, Parkinsonism induced by poisoning orpost-traumatic Parkinson's disease.
 50. A use or method according toclaim 47 wherein the movement disorder is progressive supernuclearpalsy, Huntingtons disease, multiple system atrophy, corticobasaldegeneration, Wilsons disease, Hallerrorden-Spatz disease, progressivepallidal atrophy, Dopa-responsive dystonia-Parkinsonism, spasticity orother disorders of the basal ganglia which result in dyskinesias.
 51. Ause or method according to any one of claims 47 to 50 wherein thecompound of formula (I) is in combination with one or more additionaldrugs useful in the treatment of movement disorders, the componentsbeing in the same formulation or in separate formulations foradministration simultaneously or sequentially.
 52. A use or methodaccording to claim 51 wherein said additional drug(s) useful in thetreatment of movement disorders is/are a drug useful in the treatment ofParkinson's disease.
 53. A use or method according to claim 51 or 52wherein the or one of the additional drugs is L-DOPA or a dopamineagonist.
 54. A use or method according to any one of claims 1 to 46wherein said disorder is depression, cognitive or memory impairment,acute or chronic pain, ADHD or narcolepsy.
 55. A use or method accordingto claim 54 wherein said cognitive or memory impairment disorder isAlzheimer's disease.
 56. Use of a compound as set out in any one ofclaims 1 to 42 or a pharmaceutically acceptable salt thereof in themanufacture of a medicament for neuroprotection in a subject.
 57. Amethod of neuroprotection comprising administration to a subject in needof such treatment an effective dose of a compound as set out in any oneof claims 1 to 42 or a pharmaceutically acceptable salt thereof.
 58. Ause or method according to claim 56 or 57 wherein said medicament orsaid method is for neuroprotection in a subject suffering from or atrisk from a neurodegenerative disorder.
 59. A use or method according toclaim 58 wherein said neurodegenerative disorder is a movement disorder.60. A use or method according to claim 59 wherein said movement disorderis a disorder as set out in claim 48, 49 or
 50. 61. A use or methodaccording to any one of claims 1 to 60 wherein the subject is human. 62.A compound as set out in any one of claims 1 to 42, or apharmaceutically acceptable salt or prodrug thereof, for use in therapy.63. A compound as set out in any one of claims 1 to 42, per se, otherthan compounds wherein R₁ is H and R₃ is methyl.
 64. A compoundaccording to claim 63 other than compounds wherein R₃ is methyl.